chr19-17276445-G-A

Variant names:

• chr19-17276445-G-A
• rs61634114
• NM_014173.4:c.570-50G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_014173.4(BABAM1):​c.570-50G>A 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 1,560,662 control chromosomes in the GnomAD database, including 24,334 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 0.16 (2113 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22221 hom.)
• Consequence: BABAM1 NM_014173.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.653
• Publications: 10 publications found

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]

ENSG00000269307 (HGNC:):

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

Our verdict: Benign. The variant received -8 ACMG points.

• 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 rank	MANE	Protein	UniProt
BABAM1	NM_014173.4	c.570-50G>A		intron_variant	Intron 6 of 8	ENST00000598188.6	NP_054892.2
BABAM1	NM_001033549.3	c.570-50G>A		intron_variant	Intron 6 of 8		NP_001028721.1
BABAM1	NM_001288756.2	c.570-50G>A		intron_variant	Intron 6 of 8		NP_001275685.1
BABAM1	NM_001288757.2	c.345-50G>A		intron_variant	Intron 3 of 5		NP_001275686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BABAM1	ENST00000598188.6	c.570-50G>A		intron_variant	Intron 6 of 8	1	NM_014173.4	ENSP00000471605.1
ENSG00000269307	ENST00000596542.1	n.*184-50G>A		intron_variant	Intron 5 of 9	2		ENSP00000469159.2

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24247 AN: 151922 Hom.: 2114 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.0848

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.152

GnomAD2 exomes AF: 0.145 AC: 24702 AN: 170148 AF XY: 0.147

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.0815

Gnomad ASJ exome AF: 0.158

Gnomad EAS exome AF: 0.000666

Gnomad FIN exome AF: 0.243

Gnomad NFE exome AF: 0.178

Gnomad OTH exome AF: 0.154

GnomAD4 exome AF: 0.173 AC: 243646 AN: 1408622 Hom.: 22221 Cov.: 32 AF XY: 0.172 AC XY: 119744 AN XY: 695872

African (AFR) AF: 0.136 AC: 4345 AN: 31948

American (AMR) AF: 0.0842 AC: 3116 AN: 37016

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 4230 AN: 25102

East Asian (EAS) AF: 0.000551 AC: 20 AN: 36320

South Asian (SAS) AF: 0.119 AC: 9469 AN: 79792

European-Finnish (FIN) AF: 0.238 AC: 11782 AN: 49504

Middle Eastern (MID) AF: 0.0987 AC: 563 AN: 5702

European-Non Finnish (NFE) AF: 0.185 AC: 200888 AN: 1084796

Other (OTH) AF: 0.158 AC: 9233 AN: 58442

GnomAD4 genome AF: 0.159 AC: 24240 AN: 152040 Hom.: 2113 Cov.: 32 AF XY: 0.158 AC XY: 11706 AN XY: 74296

African (AFR) AF: 0.143 AC: 5941 AN: 41472

American (AMR) AF: 0.102 AC: 1565 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 583 AN: 3468

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5172

South Asian (SAS) AF: 0.107 AC: 516 AN: 4826

European-Finnish (FIN) AF: 0.238 AC: 2515 AN: 10574

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12695 AN: 67940

Other (OTH) AF: 0.149 AC: 315 AN: 2112

Alfa AF: 0.175 Hom.: 1496

Bravo AF: 0.148

Asia WGS AF: 0.0540 AC: 189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.6
DANN	Benign	0.67
PhyloP100		0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: -12

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs61634114; hg19: chr19-17387254;