chr16-89803353-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000135.4(FANCA):c.710-12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 1,612,118 control chromosomes in the GnomAD database, including 350,575 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 41010 hom., cov: 32)

Exomes 𝑓: 0.64 ( 309565 hom. )

Consequence

FANCA
NM_000135.4 intron

Scores

Splicing: ADA: 0.0001637

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.95

Publications

29 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 16-89803353-T-C is Benign according to our data. Variant chr16-89803353-T-C is described in ClinVar as Benign. ClinVar VariationId is 255269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FANCA	NM_000135.4	MANE Select	c.710-12A>G	intron	N/A	NP_000126.2	O15360-1
FANCA	NM_001286167.3		c.710-12A>G	intron	N/A	NP_001273096.1	O15360-3
FANCA	NM_001018112.3		c.710-12A>G	intron	N/A	NP_001018122.1	O15360-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FANCA	ENST00000389301.8	TSL:1 MANE Select	c.710-12A>G	intron	N/A	ENSP00000373952.3	O15360-1
FANCA	ENST00000563673.5	TSL:1	c.710-12A>G	intron	N/A	ENSP00000456443.1	H3BRX3
FANCA	ENST00000534992.5	TSL:1	c.710-12A>G	intron	N/A	ENSP00000443675.1	F5H8D5

Frequencies

GnomAD3 genomes

AF:

0.717

AC:

109012

AN:

151996

Hom.:

40949

Cov.:

show subpopulations

Gnomad AFR

AF:

0.917

Gnomad AMI

AF:

0.479

Gnomad AMR

AF:

0.695

Gnomad ASJ

AF:

0.518

Gnomad EAS

AF:

0.987

Gnomad SAS

AF:

0.815

Gnomad FIN

AF:

0.676

Gnomad MID

AF:

0.585

Gnomad NFE

AF:

0.595

Gnomad OTH

AF:

0.665

GnomAD2 exomes

AF:

0.699

AC:

175544

AN:

251232

AF XY:

0.692

show subpopulations

Gnomad AFR exome

AF:

0.923

Gnomad AMR exome

AF:

0.783

Gnomad ASJ exome

AF:

0.521

Gnomad EAS exome

AF:

0.989

Gnomad FIN exome

AF:

0.680

Gnomad NFE exome

AF:

0.590

Gnomad OTH exome

AF:

0.642

GnomAD4 exome

AF:

0.644

AC:

940548

AN:

1460004

Hom.:

309565

Cov.:

AF XY:

0.647

AC XY:

469764

AN XY:

726362

show subpopulations

African (AFR)

AF:

0.926

AC:

30963

AN:

33442

American (AMR)

AF:

0.773

AC:

34567

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.524

AC:

13687

AN:

26112

East Asian (EAS)

AF:

0.983

AC:

38992

AN:

39686

South Asian (SAS)

AF:

0.796

AC:

68658

AN:

86234

European-Finnish (FIN)

AF:

0.670

AC:

35782

AN:

53372

Middle Eastern (MID)

AF:

0.651

AC:

3755

AN:

5766

European-Non Finnish (NFE)

AF:

0.608

AC:

674720

AN:

1110346

Other (OTH)

AF:

0.653

AC:

39424

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

17005

34010

51014

68019

85024

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18576

37152

55728

74304

92880

<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:

0.717

AC:

109134

AN:

152114

Hom.:

41010

Cov.:

AF XY:

0.725

AC XY:

53920

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.917

AC:

38081

AN:

41546

American (AMR)

AF:

0.695

AC:

10603

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.518

AC:

1799

AN:

3470

East Asian (EAS)

AF:

0.986

AC:

5110

AN:

5180

South Asian (SAS)

AF:

0.815

AC:

3936

AN:

4832

European-Finnish (FIN)

AF:

0.676

AC:

7139

AN:

10554

Middle Eastern (MID)

AF:

0.595

AC:

175

AN:

294

European-Non Finnish (NFE)

AF:

0.595

AC:

40443

AN:

67960

Other (OTH)

AF:

0.669

AC:

1412

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1442

2883

4325

5766

7208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

822

1644

2466

3288

4110

<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:

0.627

Hom.:

19456

Bravo

AF:

0.729

Asia WGS

AF:

0.900

AC:

3131

AN:

3478

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)

Fanconi anemia (2)

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

6.5

(source)

DANN

Benign

0.79

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00016

dbscSNV1_RF

Benign

0.040

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over