Variant chr19-17268749-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.322

Variant links:

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]

BABAM1 links:

USHBP1 (HGNC:24058): (USH1 protein network component harmonin binding protein 1) Enables PDZ domain binding activity. [provided by Alliance of Genome Resources, Apr 2022]

USHBP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
BABAM1	NM_014173.4 linkuse as main transcript	c.-13-45C>T	intron_variant	ENST00000598188.6	NP_054892.2
BABAM1	NM_001033549.3 linkuse as main transcript	c.-51-7C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_001028721.1
BABAM1	NM_001288756.2 linkuse as main transcript	c.-13-45C>T	intron_variant		NP_001275685.1
BABAM1	NM_001288757.2 linkuse as main transcript	c.-51-7C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_001275686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BABAM1	ENST00000598188.6 linkuse as main transcript	c.-13-45C>T		intron_variant		1	NM_014173.4	ENSP00000471605	P1	Q9NWV8-1

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34161

AN:

151836

Hom.:

4469

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.188

AC XY:

124862

AN XY:

663854

show subpopulations

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.:

AF XY:

0.221

AC XY:

16388

AN XY:

74274

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over