19-17268749-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000359435.8(BABAM1):c.-51-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,507,020 control chromosomes in the GnomAD database, including 30,499 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4474 hom., cov: 31)
  • Exomes 𝑓: 0.19 (26025 hom.)
• Consequence: BABAM1 ENST00000359435.8 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003828
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.322

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-17268749-C-T is Benign according to our data. Variant chr19-17268749-C-T is described in ClinVar as [Benign]. Clinvar id is 1227766.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BABAM1	NM_014173.4	c.-13-45C>T		intron_variant		ENST00000598188.6
BABAM1	NM_001033549.3	c.-51-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
BABAM1	NM_001288756.2	c.-13-45C>T		intron_variant
BABAM1	NM_001288757.2	c.-51-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BABAM1	ENST00000598188.6	c.-13-45C>T		intron_variant		1	NM_014173.4	P1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34161 AN: 151836 Hom.: 4469 Cov.: 31

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.200

GnomAD3 exomes AF: 0.165 AC: 24626 AN: 148944 Hom.: 2483 AF XY: 0.164 AC XY: 13288 AN XY: 81130

Gnomad AFR exome AF: 0.353

Gnomad AMR exome AF: 0.0925

Gnomad ASJ exome AF: 0.177

Gnomad EAS exome AF: 0.000434

Gnomad SAS exome AF: 0.112

Gnomad FIN exome AF: 0.242

Gnomad NFE exome AF: 0.192

Gnomad OTH exome AF: 0.159

GnomAD4 exome AF: 0.190 AC: 257692 AN: 1355066 Hom.: 26025 Cov.: 30 AF XY: 0.188 AC XY: 124862 AN XY: 663854

Gnomad4 AFR exome AF: 0.356

Gnomad4 AMR exome AF: 0.0994

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.000530

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.240

Gnomad4 NFE exome AF: 0.198

Gnomad4 OTH exome AF: 0.185

GnomAD4 genome AF: 0.225 AC: 34187 AN: 151954 Hom.: 4474 Cov.: 31 AF XY: 0.221 AC XY: 16388 AN XY: 74274

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.197

Alfa AF: 0.196 Hom.: 1793

Bravo AF: 0.222

Asia WGS AF: 0.0740 AC: 260 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 23, 2021

This variant is associated with the following publications: (PMID: 26472073) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.4
Dann	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000038
dbscSNV1_RF	Benign	0.13
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.25		Position offset: 7

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

Publications

LitVar

Other links and lift over

dbSNP: rs10424178; hg19: chr19-17379558;