dbSNP rs3805476: ENSG00000253295:n.596G>A (chr5-172768089-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000733736.1(ENSG00000253295):n.596G>A variant causes a non coding transcript exon 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

ENSG00000253295
ENST00000733736.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.510

Publications

5 publications found

Variant links:

COSMIC-nc: COSV53321536

Genes affected

ENSG00000253295 (HGNC:):

ENSG00000253295 links:

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]

DUSP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DUSP1	NM_004417.4 link	c.*673C>T		downstream_gene_variant		ENST00000239223.4	NP_004408.1	P28562B4DU40

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENSG00000253295	ENST00000733736.1 link	n.596G>A	non_coding_transcript_exon_variant	Exon 5 of 5
ENSG00000253736	ENST00000523005.1 link	n.69+5041G>A	intron_variant	Intron 1 of 1	3
DUSP1	ENST00000239223.4 link	c.*673C>T	downstream_gene_variant		1	NM_004417.4	ENSP00000239223.3	P28562

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

26971

AN:

151932

Hom.:

2639

Cov.:

show subpopulations

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:

AN:

432

Hom.:

Cov.:

AF XY:

0.165

AC XY:

AN XY:

260

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.174

AC:

AN:

426

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.178

AC:

27013

AN:

152050

Hom.:

2652

Cov.:

AF XY:

0.181

AC XY:

13435

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.148

AC:

6124

AN:

41464

American (AMR)

AF:

0.225

AC:

3440

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.308

AC:

1068

AN:

3472

East Asian (EAS)

AF:

0.392

AC:

2031

AN:

5180

South Asian (SAS)

AF:

0.267

AC:

1286

AN:

4808

European-Finnish (FIN)

AF:

0.166

AC:

1754

AN:

10548

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.157

AC:

10688

AN:

67974

Other (OTH)

AF:

0.198

AC:

417

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1143

2285

3428

4570

5713

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

296

592

888

1184

1480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.150

Hom.:

737

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

(source)

DANN

Benign

0.76

PhyloP100

0.51

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over