rs114170541

Variant names:

• chr18-34820847-C-T
• rs114170541
• NM_001386795.1:c.933C>T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001386795.1(DTNA):​c.933C>T​(p.Ser311Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 1,614,110 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0083 (19 hom., cov: 32)
  • Exomes 𝑓: 0.00091 (27 hom.)
• Consequence: DTNA NM_001386795.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.709

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 18-34820847-C-T is Benign according to our data. Variant chr18-34820847-C-T is described in ClinVar as [Benign]. Clinvar id is 46428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-34820847-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.709 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00832 (1267/152240) while in subpopulation AFR AF= 0.0275 (1142/41528). AF 95% confidence interval is 0.0262. There are 19 homozygotes in gnomad4. There are 578 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1267 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNA	NM_001386795.1	c.933C>T	p.Ser311Ser	synonymous_variant	Exon 9 of 23	ENST00000444659.6	NP_001373724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNA	ENST00000444659.6	c.933C>T	p.Ser311Ser	synonymous_variant	Exon 9 of 23	5	NM_001386795.1	ENSP00000405819.2

Frequencies

GnomAD3 genomes AF: 0.00832 AC: 1265 AN: 152122 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00648

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00212 AC: 534 AN: 251448 Hom.: 14 AF XY: 0.00165 AC XY: 224 AN XY: 135898

Gnomad AFR exome AF: 0.0284

Gnomad AMR exome AF: 0.00165

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000879

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000908 AC: 1328 AN: 1461870 Hom.: 27 Cov.: 31 AF XY: 0.000788 AC XY: 573 AN XY: 727236

Gnomad4 AFR exome AF: 0.0306

Gnomad4 AMR exome AF: 0.00195

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000459

Gnomad4 OTH exome AF: 0.00250

GnomAD4 genome AF: 0.00832 AC: 1267 AN: 152240 Hom.: 19 Cov.: 32 AF XY: 0.00776 AC XY: 578 AN XY: 74456

Gnomad4 AFR AF: 0.0275

Gnomad4 AMR AF: 0.00648

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00347 Hom.: 2

Bravo AF: 0.0101

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Apr 22, 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. -

Apr 10, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

2.6% (96 alleles) in AA (ESP) -

not provided Benign:1

Feb 09, 2016

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: This c.933C>T variant affects a non-conserved nucleotide, resulting in synonymous amino acid change. 5/5 splice-site tools via Alamut predict that this variant does not affect normal splicing. This variant was found in 326/121392 control chromosomes at a frequency of 0.0026855, which is more than 106 times higher than the maximal expected frequency of a pathogenic allele (0.000025) in this gene, suggesting this variant is benign. The variant is more frequent in African population with an allele frequency of 2.8% (295/10406 chromosomes), including six homozygotes. Multiple clinical laboratories have classified this variant as benign. Taken together, this variant has been classified as Benign. -

Left ventricular noncompaction 1 Benign:1

Feb 02, 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	-0.37
CADD	Benign	8.7
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs114170541; hg19: chr18-32400811;