rs189841793

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_000135.4(FANCA):c.80-13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000804 in 1,602,378 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00077 ( 4 hom. )

Consequence

FANCA
NM_000135.4 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5O:1

Conservation

PhyloP100: -0.473

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 16-89815999-G-A is Benign according to our data. Variant chr16-89815999-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 135542.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, not_provided=1, Likely_benign=4, Benign=1}. Variant chr16-89815999-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00117 (178/152366) while in subpopulation AMR AF = 0.00464 (71/15312). AF 95% confidence interval is 0.00377. There are 2 homozygotes in GnomAd4. There are 99 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FANCA	NM_000135.4 link	c.80-13C>T	intron_variant	Intron 1 of 42	ENST00000389301.8	NP_000126.2	O15360-1
FANCA	NM_001286167.3 link	c.80-13C>T	intron_variant	Intron 1 of 42		NP_001273096.1	O15360-3
FANCA	NM_001018112.3 link	c.80-13C>T	intron_variant	Intron 1 of 10		NP_001018122.1	O15360-2
FANCA	NM_001351830.2 link	c.80-13C>T	intron_variant	Intron 1 of 9		NP_001338759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCA	ENST00000389301.8 link	c.80-13C>T		intron_variant	Intron 1 of 42	1	NM_000135.4	ENSP00000373952.3		O15360-1

Frequencies

GnomAD3 genomes

AF:

0.00118

AC:

180

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00464

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00113

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.000964

AC:

242

AN:

251132

AF XY:

0.00116

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00136

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.000766

AC:

1110

AN:

1450012

Hom.:

Cov.:

AF XY:

0.000828

AC XY:

598

AN XY:

722176

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

AC:

AN:

33210

Gnomad4 AMR exome

AF:

0.00125

AC:

AN:

44696

Gnomad4 ASJ exome

AF:

0.000192

AC:

AN:

26036

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39630

Gnomad4 SAS exome

AF:

0.000360

AC:

AN:

86038

Gnomad4 FIN exome

AF:

0.000206

AC:

AN:

53292

Gnomad4 NFE exome

AF:

0.000770

AC:

848

AN:

1101418

Gnomad4 Remaining exome

AF:

0.00122

AC:

AN:

59950

Heterozygous variant carriers

110

164

219

274

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

120

<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:

0.00117

AC:

178

AN:

152366

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.000385

AC:

0.000384615

AN:

0.000384615

Gnomad4 AMR

AF:

0.00464

AC:

0.00463689

AN:

0.00463689

Gnomad4 ASJ

AF:

0.000288

AC:

0.000288351

AN:

0.000288351

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000207

AC:

0.000207039

AN:

0.000207039

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.00112

AC:

0.00111709

AN:

0.00111709

Gnomad4 OTH

AF:

0.00142

AC:

0.00141911

AN:

0.00141911

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<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:

0.000859

Hom.:

Bravo

AF:

0.000986

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5Other:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Fanconi anemia complementation group A

Uncertain:1Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Fanconi anemia

Benign:2

Mar 18, 2021

Sema4, Sema4

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:curation

- -

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1Other:1

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Apr 28, 2021

GeneDx

Significance:Likely 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

-0.87

CADD

Benign

0.98

DANN

Benign

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=100/0

polymorphism

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over