NM_004417.4:c.600C>A

Variant names:

• chr5-172769708-G-T
• rs2431663
• NM_004417.4:c.600C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004417.4(DUSP1):​c.600C>A​(p.Ile200Ile) 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
• Publications: 29 publications found

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]

ENSG00000253736 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004417.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP1	NM_004417.4	MANE Select	c.600C>A	p.Ile200Ile	synonymous	Exon 3 of 4	NP_004408.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP1	ENST00000239223.4	TSL:1 MANE Select	c.600C>A	p.Ile200Ile	synonymous	Exon 3 of 4	ENSP00000239223.3
	ENSG00000253736	ENST00000523005.1	TSL:3	n.69+6660G>T		intron	N/A

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

GnomAD2 exomes AF: 0.938 AC: 235831 AN: 251492 AF XY: 0.945

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 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

African (AFR) AF: 0.574 AC: 19233 AN: 33480

American (AMR) AF: 0.959 AC: 42898 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.976 AC: 25496 AN: 26134

East Asian (EAS) AF: 1.00 AC: 39697 AN: 39700

South Asian (SAS) AF: 0.980 AC: 84534 AN: 86258

European-Finnish (FIN) AF: 0.951 AC: 50829 AN: 53420

Middle Eastern (MID) AF: 0.942 AC: 5431 AN: 5766

European-Non Finnish (NFE) AF: 0.952 AC: 1058150 AN: 1112010

Other (OTH) AF: 0.938 AC: 56667 AN: 60396

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

African (AFR) AF: 0.594 AC: 24644 AN: 41510

American (AMR) AF: 0.937 AC: 14342 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.973 AC: 3375 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5184 AN: 5186

South Asian (SAS) AF: 0.984 AC: 4753 AN: 4832

European-Finnish (FIN) AF: 0.952 AC: 10104 AN: 10618

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.953 AC: 64857 AN: 68032

Other (OTH) AF: 0.884 AC: 1869 AN: 2114

Alfa AF: 0.918 Hom.: 88241

Bravo AF: 0.842

Asia WGS AF: 0.974 AC: 3387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.92
PhyloP100		5.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs2431663; hg19: chr5-172196711; COSMIC: COSV108049235;