chr19-17276367-A-G

Variant names:

• chr19-17276367-A-G
• rs34084277
• NM_014173.4:c.570-128A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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 -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 rank	MANE	Protein	UniProt
BABAM1	NM_014173.4	c.570-128A>G		intron_variant	Intron 6 of 8	ENST00000598188.6	NP_054892.2
BABAM1	NM_001033549.3	c.570-128A>G		intron_variant	Intron 6 of 8		NP_001028721.1
BABAM1	NM_001288756.2	c.570-128A>G		intron_variant	Intron 6 of 8		NP_001275685.1
BABAM1	NM_001288757.2	c.345-128A>G		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.570-128A>G		intron_variant	Intron 6 of 8	1	NM_014173.4	ENSP00000471605.1
ENSG00000269307	ENST00000596542.1	n.*184-128A>G		intron_variant	Intron 5 of 9	2		ENSP00000469159.2

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

GnomAD2 exomes AF: 0.138 AC: 18093 AN: 131558 AF XY: 0.139

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 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

African (AFR) AF: 0.180 AC: 5226 AN: 28978

American (AMR) AF: 0.0860 AC: 2944 AN: 34226

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 3969 AN: 23296

East Asian (EAS) AF: 0.000573 AC: 20 AN: 34932

South Asian (SAS) AF: 0.118 AC: 8718 AN: 74090

European-Finnish (FIN) AF: 0.237 AC: 8976 AN: 37874

Middle Eastern (MID) AF: 0.101 AC: 543 AN: 5378

European-Non Finnish (NFE) AF: 0.184 AC: 178653 AN: 968824

Other (OTH) AF: 0.160 AC: 8585 AN: 53562

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

African (AFR) AF: 0.183 AC: 7573 AN: 41484

American (AMR) AF: 0.107 AC: 1627 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 596 AN: 3468

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5176

South Asian (SAS) AF: 0.106 AC: 510 AN: 4816

European-Finnish (FIN) AF: 0.238 AC: 2511 AN: 10564

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

European-Non Finnish (NFE) AF: 0.187 AC: 12689 AN: 67928

Other (OTH) AF: 0.157 AC: 331 AN: 2104

Alfa AF: 0.176 Hom.: 1299

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
PhyloP100		-0.11
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

Other links and lift over

dbSNP: rs34084277; hg19: chr19-17387176;