rs1800331

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.1143G>T(p.Thr381Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0772 in 1,614,114 control chromosomes in the GnomAD database, including 5,724 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T381T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.061 ( 419 hom., cov: 32)

Exomes 𝑓: 0.079 ( 5305 hom. )

Consequence

FANCA
NM_000135.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -3.99

Publications

23 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: Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen, G2P, Myriad Women’s Health
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=-0.76).

BP6

Variant 16-89792009-C-A is Benign according to our data. Variant chr16-89792009-C-A is described in ClinVar as Benign. ClinVar VariationId is 255231.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.99 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000135.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCA	NM_000135.4	MANE Select	c.1143G>T	p.Thr381Thr	synonymous	Exon 13 of 43	NP_000126.2	O15360-1
	FANCA	NM_001286167.3		c.1143G>T	p.Thr381Thr	synonymous	Exon 13 of 43	NP_001273096.1	O15360-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FANCA	ENST00000389301.8	TSL:1 MANE Select	c.1143G>T	p.Thr381Thr	synonymous	Exon 13 of 43	ENSP00000373952.3	O15360-1
FANCA	ENST00000567205.2	TSL:1	n.1143G>T		non_coding_transcript_exon	Exon 13 of 27	ENSP00000457027.2	H3BT53
FANCA	ENST00000564475.6	TSL:2	c.1143G>T	p.Thr381Thr	synonymous	Exon 13 of 42	ENSP00000454977.2	H3BNS0

Frequencies

GnomAD3 genomes

AF:

0.0608

AC:

9247

AN:

152164

Hom.:

418

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0193

Gnomad AMI

AF:

0.0231

Gnomad AMR

AF:

0.0362

Gnomad ASJ

AF:

0.0577

Gnomad EAS

AF:

0.215

Gnomad SAS

AF:

0.0259

Gnomad FIN

AF:

0.0609

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0833

Gnomad OTH

AF:

0.0565

GnomAD2 exomes

AF:

0.0667

AC:

16775

AN:

251466

AF XY:

0.0658

show subpopulations

Gnomad AFR exome

AF:

0.0180

Gnomad AMR exome

AF:

0.0188

Gnomad ASJ exome

AF:

0.0587

Gnomad EAS exome

AF:

0.232

Gnomad FIN exome

AF:

0.0584

Gnomad NFE exome

AF:

0.0767

Gnomad OTH exome

AF:

0.0572

GnomAD4 exome

AF:

0.0789

AC:

115293

AN:

1461832

Hom.:

5305

Cov.:

AF XY:

0.0773

AC XY:

56218

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.0154

AC:

517

AN:

33480

American (AMR)

AF:

0.0208

AC:

929

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0570

AC:

1490

AN:

26136

East Asian (EAS)

AF:

0.156

AC:

6202

AN:

39700

South Asian (SAS)

AF:

0.0220

AC:

1899

AN:

86258

European-Finnish (FIN)

AF:

0.0572

AC:

3058

AN:

53418

Middle Eastern (MID)

AF:

0.0130

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0864

AC:

96118

AN:

1111954

Other (OTH)

AF:

0.0829

AC:

5005

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

6293

12585

18878

25170

31463

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3582

7164

10746

14328

17910

<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:

0.0608

AC:

9257

AN:

152282

Hom.:

419

Cov.:

AF XY:

0.0587

AC XY:

4368

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0193

AC:

803

AN:

41566

American (AMR)

AF:

0.0362

AC:

553

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0577

AC:

200

AN:

3468

East Asian (EAS)

AF:

0.216

AC:

1119

AN:

5178

South Asian (SAS)

AF:

0.0267

AC:

129

AN:

4830

European-Finnish (FIN)

AF:

0.0609

AC:

647

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0833

AC:

5664

AN:

68018

Other (OTH)

AF:

0.0568

AC:

120

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

449

899

1348

1798

2247

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<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:

0.0670

Hom.:

676

Bravo

AF:

0.0586

Asia WGS

AF:

0.113

AC:

391

AN:

3478

EpiCase

AF:

0.0746

EpiControl

AF:

0.0724

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Fanconi anemia complementation group A (5)

not specified (3)

not provided (2)

Fanconi anemia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.015

(source)

DANN

Benign

0.28

PhyloP100

-4.0

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over