rs17352824

Variant names:

• chr4-83476467-G-A
• rs17352824
• NM_139076.3:c.215+176C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.338
• Publications: 4 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139076.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABRAXAS1	NM_139076.3	MANE Select	c.215+176C>T		intron	N/A	NP_620775.2
	ABRAXAS1	NM_001345962.2		c.-46+176C>T		intron	N/A	NP_001332891.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABRAXAS1	ENST00000321945.12	TSL:1 MANE Select	c.215+176C>T		intron	N/A	ENSP00000369857.3
	ABRAXAS1	ENST00000506553.5	TSL:5	c.68+176C>T		intron	N/A	ENSP00000426763.1
	ABRAXAS1	ENST00000505489.5	TSL:5	c.194+176C>T		intron	N/A	ENSP00000480277.1

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89570 AN: 151812 Hom.: 27598 Cov.: 31

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.: 31 AF XY: 0.593 AC XY: 44002 AN XY: 74222

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

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.48
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17352824; hg19: chr4-84397620; COSMIC: COSV58948548; COSMIC: COSV58948548;