rs10420922

Positions:

• chr19-17271696-A-T

Variant summary

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

The ENST00000598188.6(BABAM1):​c.344+41A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,601,852 control chromosomes in the GnomAD database, including 157,795 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 0.49 (19710 hom., cov: 31)
  • Exomes 𝑓: 0.43 (138085 hom.)
• Consequence: BABAM1 ENST00000598188.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.594

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BABAM1	NM_014173.4	c.344+41A>T		intron_variant		ENST00000598188.6	NP_054892.2
BABAM1	NM_001033549.3	c.344+41A>T		intron_variant			NP_001028721.1
BABAM1	NM_001288756.2	c.344+41A>T		intron_variant			NP_001275685.1
BABAM1	NM_001288757.2	c.344+41A>T		intron_variant			NP_001275686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BABAM1	ENST00000598188.6	c.344+41A>T		intron_variant		1	NM_014173.4	ENSP00000471605	P1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75011 AN: 151838 Hom.: 19690 Cov.: 31

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.458

GnomAD3 exomes AF: 0.425 AC: 102945 AN: 242422 Hom.: 22682 AF XY: 0.422 AC XY: 55570 AN XY: 131604

Gnomad AFR exome AF: 0.692

Gnomad AMR exome AF: 0.328

Gnomad ASJ exome AF: 0.388

Gnomad EAS exome AF: 0.314

Gnomad SAS exome AF: 0.381

Gnomad FIN exome AF: 0.522

Gnomad NFE exome AF: 0.434

Gnomad OTH exome AF: 0.407

GnomAD4 exome AF: 0.432 AC: 626840 AN: 1449894 Hom.: 138085 Cov.: 30 AF XY: 0.430 AC XY: 310326 AN XY: 721414

Gnomad4 AFR exome AF: 0.696

Gnomad4 AMR exome AF: 0.335

Gnomad4 ASJ exome AF: 0.389

Gnomad4 EAS exome AF: 0.313

Gnomad4 SAS exome AF: 0.379

Gnomad4 FIN exome AF: 0.512

Gnomad4 NFE exome AF: 0.435

Gnomad4 OTH exome AF: 0.426

GnomAD4 genome AF: 0.494 AC: 75067 AN: 151958 Hom.: 19710 Cov.: 31 AF XY: 0.490 AC XY: 36399 AN XY: 74248

Gnomad4 AFR AF: 0.676

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.319

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.454

Alfa AF: 0.458 Hom.: 2815

Bravo AF: 0.490

Asia WGS AF: 0.361 AC: 1256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.22
DANN	Benign	0.48

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: rs10420922; hg19: chr19-17382505; COSMIC: COSV63921517; COSMIC: COSV63921517;