ENST00000523005.1:n.69+4822C>T

Variant names:

• chr5-172767870-C-T
• rs322351
• ENST00000523005.1:n.69+4822C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000523005.1(ENSG00000253736):​n.69+4822C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,982 control chromosomes in the GnomAD database, including 11,810 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 0.37 (11810 hom., cov: 31)
• Consequence: ENSG00000253736 ENST00000523005.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.88
• Publications: 11 publications found

Genes affected

ENSG00000253736 (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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUSP1	NM_004417.4	c.*892G>A		downstream_gene_variant		ENST00000239223.4	NP_004408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000253736	ENST00000523005.1	n.69+4822C>T		intron_variant	Intron 1 of 1	3
ENSG00000253295	ENST00000733736.1	n.462-85C>T		intron_variant	Intron 4 of 4
DUSP1	ENST00000239223.4	c.*892G>A		downstream_gene_variant		1	NM_004417.4	ENSP00000239223.3

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56712 AN: 151864 Hom.: 11806 Cov.: 31

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.401

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

GnomAD4 genome AF: 0.373 AC: 56727 AN: 151982 Hom.: 11810 Cov.: 31 AF XY: 0.373 AC XY: 27726 AN XY: 74288

African (AFR) AF: 0.179 AC: 7440 AN: 41470

American (AMR) AF: 0.391 AC: 5972 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1589 AN: 3468

East Asian (EAS) AF: 0.266 AC: 1377 AN: 5172

South Asian (SAS) AF: 0.409 AC: 1967 AN: 4812

European-Finnish (FIN) AF: 0.464 AC: 4880 AN: 10526

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32165 AN: 67954

Other (OTH) AF: 0.395 AC: 835 AN: 2112

Alfa AF: 0.439 Hom.: 19404

Bravo AF: 0.361

Asia WGS AF: 0.310 AC: 1083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.65
PhyloP100		-3.9

Splicing

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

Other links and lift over

dbSNP: rs322351; hg19: chr5-172194873;