chr19-17273458-G-A

Variant names:

• chr19-17273458-G-A
• rs3745185
• NM_014173.4:c.345-446G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014173.4(BABAM1):​c.345-446G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 151,890 control chromosomes in the GnomAD database, including 10,678 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 0.36 (10678 hom., cov: 31)
• Consequence: BABAM1 NM_014173.4 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]

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BABAM1	NM_014173.4	c.345-446G>A		intron_variant	Intron 3 of 8	ENST00000598188.6	NP_054892.2
BABAM1	NM_001033549.3	c.345-446G>A		intron_variant	Intron 3 of 8		NP_001028721.1
BABAM1	NM_001288756.2	c.345-446G>A		intron_variant	Intron 3 of 8		NP_001275685.1
BABAM1	NM_001288757.2	c.344+1803G>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.345-446G>A		intron_variant	Intron 3 of 8	1	NM_014173.4	ENSP00000471605.1
ENSG00000269307	ENST00000596542.1	n.286-446G>A		intron_variant	Intron 2 of 9	2		ENSP00000469159.2

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54755 AN: 151772 Hom.: 10671 Cov.: 31

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.361 AC: 54781 AN: 151890 Hom.: 10678 Cov.: 31 AF XY: 0.360 AC XY: 26754 AN XY: 74246

African (AFR) AF: 0.222 AC: 9193 AN: 41416

American (AMR) AF: 0.367 AC: 5587 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1504 AN: 3468

East Asian (EAS) AF: 0.140 AC: 726 AN: 5180

South Asian (SAS) AF: 0.430 AC: 2073 AN: 4818

European-Finnish (FIN) AF: 0.408 AC: 4291 AN: 10524

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 30063 AN: 67940

Other (OTH) AF: 0.374 AC: 789 AN: 2110

Alfa AF: 0.431 Hom.: 11516

Bravo AF: 0.349

Asia WGS AF: 0.316 AC: 1098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.26
DANN	Benign	0.30
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

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: rs3745185; hg19: chr19-17384267;