rs8170

chr19-17278895-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_014173.4(BABAM1):c.837G>A(p.Lys279=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,613,148 control chromosomes in the GnomAD database, including 25,760 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 0.17 (2472 hom., cov: 32)
  • Exomes 𝑓: 0.17 (23288 hom.)
• Consequence: BABAM1 NM_014173.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.06

Genes affected

BABAM1 (HGNC:25008): (BRISC and BRCA1 A complex member 1) Involved in several processes, including mitotic G2 DNA damage checkpoint signaling; positive regulation of DNA repair; and protein K63-linked deubiquitination. Located in cytosol and nuclear body. Part of BRCA1-A complex and BRISC complex. [provided by Alliance of Genome Resources, Apr 2022]

USHBP1 (HGNC:24058): (USH1 protein network component harmonin binding protein 1) Enables PDZ domain binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=3.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BABAM1	NM_014173.4	c.837G>A	p.Lys279=	synonymous_variant	9/9	ENST00000598188.6
BABAM1	NM_001033549.3	c.837G>A	p.Lys279=	synonymous_variant	9/9
BABAM1	NM_001288756.2	c.837G>A	p.Lys279=	synonymous_variant	9/9
BABAM1	NM_001288757.2	c.612G>A	p.Lys204=	synonymous_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BABAM1	ENST00000598188.6	c.837G>A	p.Lys279=	synonymous_variant	9/9	1	NM_014173.4	P1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26386 AN: 152088 Hom.: 2466 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.163

GnomAD3 exomes AF: 0.149 AC: 36995 AN: 247668 Hom.: 3234 AF XY: 0.151 AC XY: 20338 AN XY: 134626

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.0800

Gnomad ASJ exome AF: 0.162

Gnomad EAS exome AF: 0.000613

Gnomad SAS exome AF: 0.115

Gnomad FIN exome AF: 0.241

Gnomad NFE exome AF: 0.179

Gnomad OTH exome AF: 0.151

GnomAD4 exome AF: 0.174 AC: 253709 AN: 1460942 Hom.: 23288 Cov.: 33 AF XY: 0.173 AC XY: 125471 AN XY: 726676

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.0837

Gnomad4 ASJ exome AF: 0.172

Gnomad4 EAS exome AF: 0.000504

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.238

Gnomad4 NFE exome AF: 0.185

Gnomad4 OTH exome AF: 0.162

GnomAD4 genome AF: 0.174 AC: 26410 AN: 152206 Hom.: 2472 Cov.: 32 AF XY: 0.171 AC XY: 12751 AN XY: 74390

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.161

Alfa AF: 0.172 Hom.: 5834

Bravo AF: 0.164

Asia WGS AF: 0.0610 AC: 215 AN: 3478

EpiCase AF: 0.175

EpiControl AF: 0.170

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	11
Dann	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs8170; hg19: chr19-17389704; COSMIC: COSV63920809; COSMIC: COSV63920809;