5-172769708-G-T

Position:

• chr5-172769708-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004417.4(DUSP1):​c.600C>A​(p.Ile200=) variant causes a synonymous change. The variant allele was found at a frequency of 0.937 in 1,614,160 control chromosomes in the GnomAD database, including 714,491 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 0.86 (57746 hom., cov: 34)
  • Exomes 𝑓: 0.95 (656745 hom.)
• Consequence: DUSP1 NM_004417.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.81

Genes affected

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP1	NM_004417.4	c.600C>A	p.Ile200=	synonymous_variant	3/4	ENST00000239223.4	NP_004408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP1	ENST00000239223.4	c.600C>A	p.Ile200=	synonymous_variant	3/4	1	NM_004417.4	ENSP00000239223	P1
	ENST00000523005.1	n.69+6660G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130227 AN: 152154 Hom.: 57720 Cov.: 34

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.937

Gnomad ASJ AF: 0.973

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.983

Gnomad FIN AF: 0.952

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.953

Gnomad OTH AF: 0.883

GnomAD3 exomes AF: 0.938 AC: 235831 AN: 251492 Hom.: 111680 AF XY: 0.945 AC XY: 128438 AN XY: 135920

Gnomad AFR exome AF: 0.589

Gnomad AMR exome AF: 0.962

Gnomad ASJ exome AF: 0.976

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.981

Gnomad FIN exome AF: 0.951

Gnomad NFE exome AF: 0.952

Gnomad OTH exome AF: 0.949

GnomAD4 exome AF: 0.946 AC: 1382935 AN: 1461888 Hom.: 656745 Cov.: 73 AF XY: 0.948 AC XY: 689587 AN XY: 727248

Gnomad4 AFR exome AF: 0.574

Gnomad4 AMR exome AF: 0.959

Gnomad4 ASJ exome AF: 0.976

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.980

Gnomad4 FIN exome AF: 0.951

Gnomad4 NFE exome AF: 0.952

Gnomad4 OTH exome AF: 0.938

GnomAD4 genome AF: 0.856 AC: 130296 AN: 152272 Hom.: 57746 Cov.: 34 AF XY: 0.860 AC XY: 63995 AN XY: 74452

Gnomad4 AFR AF: 0.594

Gnomad4 AMR AF: 0.937

Gnomad4 ASJ AF: 0.973

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.984

Gnomad4 FIN AF: 0.952

Gnomad4 NFE AF: 0.953

Gnomad4 OTH AF: 0.884

Alfa AF: 0.921 Hom.: 75576

Bravo AF: 0.842

Asia WGS AF: 0.974 AC: 3387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.92

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: rs2431663; hg19: chr5-172196711;