chr4-83472232-T-A

Variant names:

• chr4-83472232-T-A
• rs767146349
• NM_139076.3:c.272A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_139076.3(ABRAXAS1):​c.272A>T​(p.Asn91Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,521,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N91D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000080 (0 hom.)
• Consequence: ABRAXAS1 NM_139076.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 0.164
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.059451073).

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.272A>T	p.Asn91Ile	missense	Exon 4 of 9	NP_620775.2	Q6UWZ7-1
	ABRAXAS1	NM_001345962.2		c.-45-1836A>T		intron	N/A	NP_001332891.1	Q6UWZ7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABRAXAS1	ENST00000321945.12	TSL:1 MANE Select	c.272A>T	p.Asn91Ile	missense	Exon 4 of 9	ENSP00000369857.3	Q6UWZ7-1
	ABRAXAS1	ENST00000856950.1		c.272A>T	p.Asn91Ile	missense	Exon 4 of 9	ENSP00000527009.1
	ABRAXAS1	ENST00000856949.1		c.272A>T	p.Asn91Ile	missense	Exon 4 of 8	ENSP00000527008.1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152236 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000137 AC: 2 AN: 145924 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000109

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000804 AC: 11 AN: 1369002 Hom.: 0 Cov.: 26 AF XY: 0.00000592 AC XY: 4 AN XY: 675868

African (AFR) AF: 0.00 AC: 0 AN: 29624

American (AMR) AF: 0.000267 AC: 8 AN: 29996

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24690

East Asian (EAS) AF: 0.00 AC: 0 AN: 35036

South Asian (SAS) AF: 0.00 AC: 0 AN: 72216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49186

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5562

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1066066

Other (OTH) AF: 0.0000530 AC: 3 AN: 56626

GnomAD4 genome AF: 0.000145 AC: 22 AN: 152236 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74376

African (AFR) AF: 0.000169 AC: 7 AN: 41466

American (AMR) AF: 0.000851 AC: 13 AN: 15284

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000212

ExAC AF: 0.00000900 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	not specified (2)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.57
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.16
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.042
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.010	D
Polyphen		0.20	B
Vest4		0.34
MVP		0.36
MPC		0.21
ClinPred		0.16	T
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.98
Varity_R		0.24
gMVP		0.35
Mutation Taster		=84/16	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

Other links and lift over

dbSNP: rs767146349; hg19: chr4-84393385;