rs1800358

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000135.4(FANCA):c.3654A>G(p.Pro1218Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,613,748 control chromosomes in the GnomAD database, including 9,353 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1498 hom., cov: 32)

Exomes 𝑓: 0.098 ( 7855 hom. )

Consequence

FANCA
NM_000135.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.82

Publications

17 publications found

Variant links:

Genes affected

FANCA (HGNC:3582): (FA complementation group A) The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group A. Alternative splicing results in multiple transcript variants encoding different isoforms. Mutations in this gene are the most common cause of Fanconi anemia. [provided by RefSeq, Jul 2008]

FANCA Gene-Disease associations (from GenCC):

Fanconi anemia complementation group A
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, G2P
Fanconi anemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

FANCA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 16-89742911-T-C is Benign according to our data. Variant chr16-89742911-T-C is described in ClinVar as Benign. ClinVar VariationId is 255261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.82 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCA	NM_000135.4 link	c.3654A>G	p.Pro1218Pro	synonymous_variant	Exon 37 of 43	ENST00000389301.8	NP_000126.2	O15360-1
FANCA	NM_001286167.3 link	c.3654A>G	p.Pro1218Pro	synonymous_variant	Exon 37 of 43		NP_001273096.1	O15360-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCA	ENST00000389301.8 link	c.3654A>G	p.Pro1218Pro	synonymous_variant	Exon 37 of 43	1	NM_000135.4	ENSP00000373952.3		O15360-1

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19285

AN:

152034

Hom.:

1494

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0634

Gnomad ASJ

AF:

0.0857

Gnomad EAS

AF:

0.222

Gnomad SAS

AF:

0.122

Gnomad FIN

AF:

0.0849

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0944

Gnomad OTH

AF:

0.108

GnomAD2 exomes

AF:

0.101

AC:

25429

AN:

251310

AF XY:

0.0999

show subpopulations

Gnomad AFR exome

AF:

0.213

Gnomad AMR exome

AF:

0.0349

Gnomad ASJ exome

AF:

0.0819

Gnomad EAS exome

AF:

0.235

Gnomad FIN exome

AF:

0.0841

Gnomad NFE exome

AF:

0.0882

Gnomad OTH exome

AF:

0.0822

GnomAD4 exome

AF:

0.0982

AC:

143511

AN:

1461596

Hom.:

7855

Cov.:

AF XY:

0.0982

AC XY:

71378

AN XY:

727124

show subpopulations

African (AFR)

AF:

0.216

AC:

7229

AN:

33476

American (AMR)

AF:

0.0386

AC:

1725

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0810

AC:

2118

AN:

26136

East Asian (EAS)

AF:

0.165

AC:

6553

AN:

39656

South Asian (SAS)

AF:

0.106

AC:

9166

AN:

86246

European-Finnish (FIN)

AF:

0.0806

AC:

4304

AN:

53390

Middle Eastern (MID)

AF:

0.0732

AC:

422

AN:

5768

European-Non Finnish (NFE)

AF:

0.0947

AC:

105295

AN:

1111834

Other (OTH)

AF:

0.111

AC:

6699

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

6476

12953

19429

25906

32382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4048

8096

12144

16192

20240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.127

AC:

19312

AN:

152152

Hom.:

1498

Cov.:

AF XY:

0.124

AC XY:

9249

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.210

AC:

8720

AN:

41500

American (AMR)

AF:

0.0632

AC:

965

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.0857

AC:

297

AN:

3466

East Asian (EAS)

AF:

0.223

AC:

1155

AN:

5172

South Asian (SAS)

AF:

0.122

AC:

590

AN:

4820

European-Finnish (FIN)

AF:

0.0849

AC:

900

AN:

10604

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0943

AC:

6416

AN:

68006

Other (OTH)

AF:

0.107

AC:

227

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

829

1657

2486

3314

4143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

216

432

648

864

1080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.104

Hom.:

514

Bravo

AF:

0.128

Asia WGS

AF:

0.177

AC:

614

AN:

3478

EpiCase

AF:

0.0899

EpiControl

AF:

0.0879

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group A

Benign:5

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 15, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 08, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 06, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Fanconi anemia

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.016

(source)

DANN

Benign

0.27

PhyloP100

-1.8

PromoterAI

-0.023

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over