rs4283892

Positions:

• chr6-56501016-A-G
• chr6-56501016-A-T

Variant summary

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

The NM_001374736.1(DST):​c.19896+64T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 1,495,330 control chromosomes in the GnomAD database, including 406,943 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.75 (43559 hom., cov: 32)
  • Exomes 𝑓: 0.73 (363384 hom.)
• Consequence: DST NM_001374736.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.68

Genes affected

DST (HGNC:1090): (dystonin) This gene encodes a member of the plakin protein family of adhesion junction plaque proteins. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the full-length nature of some variants has not been defined. It has been reported that some isoforms are expressed in neural and muscle tissue, anchoring neural intermediate filaments to the actin cytoskeleton, and some isoforms are expressed in epithelial tissue, anchoring keratin-containing intermediate filaments to hemidesmosomes. Consistent with the expression, mice defective for this gene show skin blistering and neurodegeneration. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 6-56501016-A-G is Benign according to our data. Variant chr6-56501016-A-G is described in ClinVar as [Benign]. Clinvar id is 1288438.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DST	NM_001374736.1	c.19896+64T>C		intron_variant		ENST00000680361.1	NP_001361665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DST	ENST00000680361.1	c.19896+64T>C		intron_variant			NM_001374736.1	ENSP00000505098.1

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114547 AN: 152004 Hom.: 43513 Cov.: 32

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.692

GnomAD4 exome AF: 0.734 AC: 985892 AN: 1343208 Hom.: 363384 AF XY: 0.731 AC XY: 485957 AN XY: 664464

Gnomad4 AFR exome AF: 0.825

Gnomad4 AMR exome AF: 0.731

Gnomad4 ASJ exome AF: 0.615

Gnomad4 EAS exome AF: 0.758

Gnomad4 SAS exome AF: 0.681

Gnomad4 FIN exome AF: 0.818

Gnomad4 NFE exome AF: 0.734

Gnomad4 OTH exome AF: 0.718

GnomAD4 genome AF: 0.754 AC: 114652 AN: 152122 Hom.: 43559 Cov.: 32 AF XY: 0.754 AC XY: 56035 AN XY: 74350

Gnomad4 AFR AF: 0.824

Gnomad4 AMR AF: 0.698

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.776

Gnomad4 SAS AF: 0.684

Gnomad4 FIN AF: 0.820

Gnomad4 NFE AF: 0.729

Gnomad4 OTH AF: 0.693

Alfa AF: 0.758 Hom.: 7195

Bravo AF: 0.747

Asia WGS AF: 0.749 AC: 2604 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

Mar 06, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.45
DANN	Benign	0.19

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: rs4283892; hg19: chr6-56365814;