rs541157

Variant names:

• chr18-34875415-T-C
• rs541157
• NM_001386795.1:c.1903+17T>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001386795.1(DTNA):​c.1903+17T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,613,804 control chromosomes in the GnomAD database, including 13,755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2251 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11504 hom.)
• Consequence: DTNA NM_001386795.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.00

Genes affected

DTNA (HGNC:3057): (dystrobrevin alpha) The protein encoded by this gene belongs to the dystrobrevin subfamily of the dystrophin family. This protein is a component of the dystrophin-associated protein complex (DPC), which consists of dystrophin and several integral and peripheral membrane proteins, including dystroglycans, sarcoglycans, syntrophins and alpha- and beta-dystrobrevin. The DPC localizes to the sarcolemma and its disruption is associated with various forms of muscular dystrophy. Mutations in this gene are associated with left ventricular noncompaction with congenital heart defects. Multiple alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 18-34875415-T-C is Benign according to our data. Variant chr18-34875415-T-C is described in ClinVar as [Benign]. Clinvar id is 137178.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNA	NM_001386795.1	c.1903+17T>C		intron_variant	Intron 18 of 22	ENST00000444659.6	NP_001373724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNA	ENST00000444659.6	c.1903+17T>C		intron_variant	Intron 18 of 22	5	NM_001386795.1	ENSP00000405819.2

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24173 AN: 152018 Hom.: 2248 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.140

GnomAD3 exomes AF: 0.119 AC: 29765 AN: 250264 Hom.: 2245 AF XY: 0.121 AC XY: 16385 AN XY: 135502

Gnomad AFR exome AF: 0.270

Gnomad AMR exome AF: 0.0610

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.0139

Gnomad SAS exome AF: 0.131

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.122

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.120 AC: 175307 AN: 1461668 Hom.: 11504 Cov.: 32 AF XY: 0.121 AC XY: 87706 AN XY: 727124

Gnomad4 AFR exome AF: 0.271

Gnomad4 AMR exome AF: 0.0664

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.00756

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.155

Gnomad4 NFE exome AF: 0.119

Gnomad4 OTH exome AF: 0.118

GnomAD4 genome AF: 0.159 AC: 24202 AN: 152136 Hom.: 2251 Cov.: 32 AF XY: 0.160 AC XY: 11889 AN XY: 74396

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.0100

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.138

Alfa AF: 0.130 Hom.: 1016

Bravo AF: 0.157

Asia WGS AF: 0.0750 AC: 261 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Jan 08, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Left ventricular noncompaction 1 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs541157; hg19: chr18-32455379;