rs532908932

Variant names:

• chr4-83484979-G-A
• rs532908932
• NM_139076.3:c.87+7C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-83484979-G-A
• chr4-83484979-G-C
• chr4-83484979-G-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_139076.3(ABRAXAS1):​c.87+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00018 in 1,572,936 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00019 (3 hom.)
• Consequence: ABRAXAS1 NM_139076.3 splice_region, intron
• Scores: Splicing: ADA: 0.02104
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.902
• Publications: 0 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.366797).
• BP6: Variant 4-83484979-G-A is Benign according to our data. Variant chr4-83484979-G-A is described in ClinVar as Benign. ClinVar VariationId is 241861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABRAXAS1	NM_139076.3	MANE Select	c.87+7C>T		splice_region intron	N/A	NP_620775.2
	ABRAXAS1	NM_001345962.2		c.-174+7C>T		splice_region intron	N/A	NP_001332891.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABRAXAS1	ENST00000321945.12	TSL:1 MANE Select	c.87+7C>T		splice_region intron	N/A	ENSP00000369857.3
	ABRAXAS1	ENST00000515303.2	TSL:1	c.-65+7C>T		splice_region intron	N/A	ENSP00000421068.1
	ABRAXAS1	ENST00000503217.2	TSL:4	c.94C>T	p.Arg32*	stop_gained	Exon 1 of 5	ENSP00000481099.1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152122 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000463 AC: 100 AN: 216118 AF XY: 0.000618

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000101

Gnomad OTH exome AF: 0.000197

GnomAD4 exome AF: 0.000195 AC: 277 AN: 1420704 Hom.: 3 Cov.: 30 AF XY: 0.000297 AC XY: 210 AN XY: 706676

African (AFR) AF: 0.00 AC: 0 AN: 29910

American (AMR) AF: 0.00 AC: 0 AN: 41624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24842

East Asian (EAS) AF: 0.0000278 AC: 1 AN: 35938

South Asian (SAS) AF: 0.00325 AC: 267 AN: 82280

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51796

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5544

European-Non Finnish (NFE) AF: 0.00000550 AC: 6 AN: 1090560

Other (OTH) AF: 0.0000515 AC: 3 AN: 58210

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152232 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74430

African (AFR) AF: 0.00 AC: 0 AN: 41548

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.000457 AC: 55

Asia WGS AF: 0.000579 AC: 2 AN: 3468

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	13
DANN	Benign	0.97
FATHMM_MKL	Benign	0.30	N
PhyloP100		0.90
GERP RS		3.3
PromoterAI		-0.0038	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.021
dbscSNV1_RF	Benign	0.12
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: rs532908932; hg19: chr4-84406132;