rs3805476

Positions:

• chr5-172768089-G-A
• chr5-172768089-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000523005.1(ENSG00000253736):​n.69+5041G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,482 control chromosomes in the GnomAD database, including 2,659 homozygotes. 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: 𝑓 0.18 (2652 hom., cov: 32)
  • Exomes 𝑓: 0.17 (7 hom.)
• Consequence: ENST00000523005.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.510

Genes affected

(HGNC:):

DUSP1 (HGNC:3064): (dual specificity phosphatase 1) The protein encoded by this gene is a phosphatase with dual specificity for tyrosine and threonine. The encoded protein can dephosphorylate MAP kinase MAPK1/ERK2, which results in its involvement in several cellular processes. This protein appears to play an important role in the human cellular response to environmental stress as well as in the negative regulation of cellular proliferation. Finally, the encoded protein can make some solid tumors resistant to both chemotherapy and radiotherapy, making it a target for cancer therapy. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DUSP1	NM_004417.4			downstream_gene_variant		ENST00000239223.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000523005.1	n.69+5041G>A		intron_variant, non_coding_transcript_variant		3
DUSP1	ENST00000239223.4			downstream_gene_variant		1	NM_004417.4	P1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 26971 AN: 151932 Hom.: 2639 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.193

GnomAD4 exome AF: 0.174 AC: 75 AN: 432 Hom.: 7 Cov.: 0 AF XY: 0.165 AC XY: 43 AN XY: 260

Gnomad4 FIN exome AF: 0.174

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.178 AC: 27013 AN: 152050 Hom.: 2652 Cov.: 32 AF XY: 0.181 AC XY: 13435 AN XY: 74320

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.198

Alfa AF: 0.143 Hom.: 563

Bravo AF: 0.179

Asia WGS AF: 0.343 AC: 1191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.1
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3805476; hg19: chr5-172195092; COSMIC: COSV53321536;