19-17268749-C-T

Variant names:

• chr19-17268749-C-T
• rs10424178
• ENST00000602066.5:c.-58C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000602066.5(BABAM1):​c.-58C>T variant causes a 5 prime UTR 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. 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 ENST00000602066.5 5_prime_UTR
• Scores: Splicing: ADA: 0.00003828
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.322
• Publications: 17 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 -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 VariationId 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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BABAM1	NM_014173.4	c.-13-45C>T		intron_variant	Intron 1 of 8	ENST00000598188.6	NP_054892.2
BABAM1	NM_001033549.3	c.-51-7C>T		splice_region_variant, intron_variant	Intron 1 of 8		NP_001028721.1
BABAM1	NM_001288756.2	c.-13-45C>T		intron_variant	Intron 1 of 8		NP_001275685.1
BABAM1	NM_001288757.2	c.-51-7C>T		splice_region_variant, intron_variant	Intron 1 of 5		NP_001275686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BABAM1	ENST00000598188.6	c.-13-45C>T		intron_variant	Intron 1 of 8	1	NM_014173.4	ENSP00000471605.1
ENSG00000269307	ENST00000596542.1	n.-13-45C>T		intron_variant	Intron 1 of 9	2		ENSP00000469159.2

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

GnomAD2 exomes AF: 0.165 AC: 24626 AN: 148944 AF XY: 0.164

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 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

African (AFR) AF: 0.356 AC: 10817 AN: 30422

American (AMR) AF: 0.0994 AC: 3026 AN: 30446

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 3848 AN: 20764

East Asian (EAS) AF: 0.000530 AC: 20 AN: 37752

South Asian (SAS) AF: 0.121 AC: 8646 AN: 71400

European-Finnish (FIN) AF: 0.240 AC: 9961 AN: 41504

Middle Eastern (MID) AF: 0.130 AC: 654 AN: 5048

European-Non Finnish (NFE) AF: 0.198 AC: 210375 AN: 1061688

Other (OTH) AF: 0.185 AC: 10345 AN: 56042

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

African (AFR) AF: 0.345 AC: 14278 AN: 41412

American (AMR) AF: 0.138 AC: 2109 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 657 AN: 3472

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5180

South Asian (SAS) AF: 0.111 AC: 537 AN: 4818

European-Finnish (FIN) AF: 0.240 AC: 2527 AN: 10534

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13540 AN: 67956

Other (OTH) AF: 0.197 AC: 416 AN: 2110

Alfa AF: 0.196 Hom.: 2597

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

Submissions by phenotype

not provided Benign:2

Feb 23, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.79
PhyloP100		-0.32
PromoterAI		-0.012	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10424178; hg19: chr19-17379558;