6-7570730-A-G

Position:

• chr6-7570730-A-G

Variant summary

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

The NM_004415.4(DSP):​c.1701+167A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 152,106 control chromosomes in the GnomAD database, including 46,264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.78 (46264 hom., cov: 32)
• Consequence: DSP NM_004415.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.466

Genes affected

DSP (HGNC:3052): (desmoplakin) This gene encodes a protein that anchors intermediate filaments to desmosomal plaques and forms an obligate component of functional desmosomes. Mutations in this gene are the cause of several cardiomyopathies and keratodermas, including skin fragility-woolly hair syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-7570730-A-G is Benign according to our data. Variant chr6-7570730-A-G is described in ClinVar as [Benign]. Clinvar id is 672133.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSP	NM_004415.4	c.1701+167A>G		intron_variant		ENST00000379802.8	NP_004406.2
DSP	NM_001008844.3	c.1701+167A>G		intron_variant			NP_001008844.1
DSP	NM_001319034.2	c.1701+167A>G		intron_variant			NP_001305963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSP	ENST00000379802.8	c.1701+167A>G		intron_variant		1	NM_004415.4	ENSP00000369129	P2
DSP	ENST00000418664.2	c.1701+167A>G		intron_variant		1		ENSP00000396591	A2
DSP	ENST00000710359.1	c.1701+167A>G		intron_variant				ENSP00000518230	A2
DSP	ENST00000684395.1	n.85+167A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118401 AN: 151988 Hom.: 46243 Cov.: 32

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.783

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.779 AC: 118469 AN: 152106 Hom.: 46264 Cov.: 32 AF XY: 0.777 AC XY: 57757 AN XY: 74368

Gnomad4 AFR AF: 0.799

Gnomad4 AMR AF: 0.789

Gnomad4 ASJ AF: 0.844

Gnomad4 EAS AF: 0.817

Gnomad4 SAS AF: 0.705

Gnomad4 FIN AF: 0.719

Gnomad4 NFE AF: 0.772

Gnomad4 OTH AF: 0.779

Alfa AF: 0.777 Hom.: 93627

Bravo AF: 0.789

Asia WGS AF: 0.708 AC: 2463 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

Jun 13, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.60

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: rs2076302; hg19: chr6-7570963;