dbSNP rs17352824: ABRAXAS1:c.215+176C>T (chr4-83476467-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_139076.3(ABRAXAS1):c.215+176C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 151,930 control chromosomes in the GnomAD database, including 27,651 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.59 ( 27651 hom., cov: 31)

Consequence

ABRAXAS1
NM_139076.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.338

Publications

4 publications found

Variant links:

Genes affected

ABRAXAS1 (HGNC:25829): (abraxas 1, BRCA1 A complex subunit) This gene encodes a protein that binds to the C-terminal repeats of breast cancer 1 (BRCA1) through a phospho-SXXF motif. The encoded protein recruits ubiquitin interaction motif containing 1 protein to BRCA1 protein and is required for DNA damage resistance, DNA repair, and cell cycle checkpoint control. Pseudogenes of this gene are found on chromosomes 3 and 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ABRAXAS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 4-83476467-G-A is Benign according to our data. Variant chr4-83476467-G-A is described in ClinVar as Benign. ClinVar VariationId is 1280562.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ABRAXAS1	NM_139076.3 link	c.215+176C>T	intron_variant	Intron 3 of 8	ENST00000321945.12	NP_620775.2	Q6UWZ7-1
ABRAXAS1	NM_001345962.2 link	c.-46+176C>T	intron_variant	Intron 3 of 7		NP_001332891.1	Q6UWZ7-2
ABRAXAS1	XR_001741334.3 link	n.243+176C>T	intron_variant	Intron 3 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABRAXAS1	ENST00000321945.12 link	c.215+176C>T		intron_variant	Intron 3 of 8	1	NM_139076.3	ENSP00000369857.3		Q6UWZ7-1

Frequencies

GnomAD3 genomes

AF:

0.590

AC:

89570

AN:

151812

Hom.:

27598

Cov.:

show subpopulations

Gnomad AFR

AF:

0.759

Gnomad AMI

AF:

0.569

Gnomad AMR

AF:

0.604

Gnomad ASJ

AF:

0.445

Gnomad EAS

AF:

0.668

Gnomad SAS

AF:

0.613

Gnomad FIN

AF:

0.511

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.499

Gnomad OTH

AF:

0.543

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.590

AC:

89688

AN:

151930

Hom.:

27651

Cov.:

AF XY:

0.593

AC XY:

44002

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.759

AC:

31464

AN:

41448

American (AMR)

AF:

0.604

AC:

9221

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.445

AC:

1541

AN:

3466

East Asian (EAS)

AF:

0.668

AC:

3447

AN:

5162

South Asian (SAS)

AF:

0.613

AC:

2951

AN:

4812

European-Finnish (FIN)

AF:

0.511

AC:

5385

AN:

10534

Middle Eastern (MID)

AF:

0.459

AC:

134

AN:

292

European-Non Finnish (NFE)

AF:

0.499

AC:

33878

AN:

67938

Other (OTH)

AF:

0.546

AC:

1150

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1754

3508

5261

7015

8769

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

746

1492

2238

2984

3730

<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:

0.565

Hom.:

3124

Bravo

AF:

0.599

Asia WGS

AF:

0.678

AC:

2352

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 18, 2021

GeneDx

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

-0.89

CADD

Benign

1.0

(source)

DANN

Benign

0.48

PhyloP100

-0.34

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over