rs4666053

Positions:

• chr2-28312194-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199191.3(BABAM2):​c.1088+13703A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 151,972 control chromosomes in the GnomAD database, including 19,617 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (19617 hom., cov: 32)
• Consequence: BABAM2 NM_199191.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350

Genes affected

BABAM2 (HGNC:1106): (BRISC and BRCA1 A complex member 2) This gene encodes an anti-apoptotic, death receptor-associated protein that interacts with tumor necrosis factor-receptor-1. The encoded protein acts as an adapter in several protein complexes, including the BRCA1-A complex and the BRISC complex. The BRCA1-A complex possesses ubiquitinase activity and targets sites of double strand DNA breaks, while the BRISC complex exhibits deubiquitinase activity and is involved in mitotic spindle assembly. This gene is upregulated in several types of cancer. [provided by RefSeq, Jun 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BABAM2	NM_199191.3	c.1088+13703A>G		intron_variant		ENST00000379624.6	NP_954661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BABAM2	ENST00000379624.6	c.1088+13703A>G		intron_variant		1	NM_199191.3	ENSP00000368945.1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76768 AN: 151852 Hom.: 19612 Cov.: 32

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.505 AC: 76818 AN: 151972 Hom.: 19617 Cov.: 32 AF XY: 0.504 AC XY: 37451 AN XY: 74234

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.564

Alfa AF: 0.526 Hom.: 7030

Bravo AF: 0.519

Asia WGS AF: 0.586 AC: 2039 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.7
DANN	Benign	0.81

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

LitVar

Other links and lift over

dbSNP: rs4666053; hg19: chr2-28535061;