rs1757982573

Variant names:

• chr6-7541846-C-G
• rs1757982573
• NM_004415.4:c.-70C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-7541846-C-G
• chr6-7541846-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004415.4(DSP):​c.-70C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000727 in 1,375,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: DSP NM_004415.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.538
• Publications: 0 publications found

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]

DSP-AS1 (HGNC:56039): (DSP antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSP	NM_004415.4	c.-70C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 24	ENST00000379802.8	NP_004406.2
DSP	NM_004415.4	c.-70C>G		5_prime_UTR_variant	Exon 1 of 24	ENST00000379802.8	NP_004406.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSP	ENST00000379802.8	c.-70C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 24	1	NM_004415.4	ENSP00000369129.3
DSP	ENST00000379802.8	c.-70C>G		5_prime_UTR_variant	Exon 1 of 24	1	NM_004415.4	ENSP00000369129.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.27e-7 AC: 1 AN: 1375470 Hom.: 0 Cov.: 29 AF XY: 0.00000148 AC XY: 1 AN XY: 676256

African (AFR) AF: 0.00 AC: 0 AN: 31084

American (AMR) AF: 0.00 AC: 0 AN: 35996

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23896

East Asian (EAS) AF: 0.00 AC: 0 AN: 35800

South Asian (SAS) AF: 0.00 AC: 0 AN: 76030

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4108

European-Non Finnish (NFE) AF: 9.35e-7 AC: 1 AN: 1069090

Other (OTH) AF: 0.00 AC: 0 AN: 56896

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.2
DANN	Benign	0.43
PhyloP100		-0.54
PromoterAI		-0.086	Neutral

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

Other links and lift over

dbSNP: rs1757982573; hg19: chr6-7542079;