chr19-17276367-A-G

Position:

• chr19-17276367-A-G

Variant summary

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

The NM_014173.4(BABAM1):​c.570-128A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,413,158 control chromosomes in the GnomAD database, including 22,299 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 (2380 hom., cov: 31)
  • Exomes 𝑓: 0.17 (19919 hom.)
• Consequence: BABAM1 NM_014173.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BABAM1	NM_014173.4	c.570-128A>G		intron_variant		ENST00000598188.6
BABAM1	NM_001033549.3	c.570-128A>G		intron_variant
BABAM1	NM_001288756.2	c.570-128A>G		intron_variant
BABAM1	NM_001288757.2	c.345-128A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BABAM1	ENST00000598188.6	c.570-128A>G		intron_variant		1	NM_014173.4	P1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25948 AN: 151880 Hom.: 2381 Cov.: 31

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.160

GnomAD3 exomes AF: 0.138 AC: 18093 AN: 131558 Hom.: 1505 AF XY: 0.139 AC XY: 9774 AN XY: 70340

Gnomad AFR exome AF: 0.184

Gnomad AMR exome AF: 0.0823

Gnomad ASJ exome AF: 0.157

Gnomad EAS exome AF: 0.000660

Gnomad SAS exome AF: 0.113

Gnomad FIN exome AF: 0.239

Gnomad NFE exome AF: 0.175

Gnomad OTH exome AF: 0.152

GnomAD4 exome AF: 0.173 AC: 217634 AN: 1261160 Hom.: 19919 Cov.: 19 AF XY: 0.171 AC XY: 107230 AN XY: 626006

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.0860

Gnomad4 ASJ exome AF: 0.170

Gnomad4 EAS exome AF: 0.000573

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.237

Gnomad4 NFE exome AF: 0.184

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome AF: 0.171 AC: 25948 AN: 151998 Hom.: 2380 Cov.: 31 AF XY: 0.169 AC XY: 12521 AN XY: 74262

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.157

Alfa AF: 0.176 Hom.: 833

Bravo AF: 0.161

Asia WGS AF: 0.0570 AC: 201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.7
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs34084277; hg19: chr19-17387176;