dbSNP rs3820449: ATF6-DT:n.373-7015C>T (chr1-161757382-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 ENST00000702792.1(ATF6-DT):n.373-7015C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,020 control chromosomes in the GnomAD database, including 3,670 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 0.20 ( 3659 hom., cov: 32)

Exomes 𝑓: 0.19 ( 11 hom. )

Consequence

ATF6-DT
ENST00000702792.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0610

Publications

8 publications found

Variant links:

Genes affected

ATF6-DT (HGNC:55826): (ATF6 divergent transcript)

ATF6-DT links:

DUSP12 (HGNC:3067): (dual specificity phosphatase 12) The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which is associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product is the human ortholog of the Saccharomyces cerevisiae YVH1 protein tyrosine phosphatase. It is localized predominantly in the nucleus, and is novel in that it contains, and is regulated by a zinc finger domain. [provided by RefSeq, Jul 2008]

DUSP12 links:

Genome browser will be placed here

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=-0.58).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUSP12	NM_007240.3 link	c.*435G>A		downstream_gene_variant		ENST00000367943.5	NP_009171.1	Q9UNI6
DUSP12	XM_005244862.4 link	c.*435G>A		downstream_gene_variant			XP_005244919.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ATF6-DT	ENST00000702792.1 link	n.373-7015C>T	intron_variant	Intron 2 of 2
ATF6-DT	ENST00000792236.1 link	n.548-515C>T	intron_variant	Intron 3 of 3
DUSP12	ENST00000367943.5 link	c.*435G>A	downstream_gene_variant		1	NM_007240.3	ENSP00000356920.4	Q9UNI6
DUSP12	ENST00000484291.5 link	n.*938G>A	downstream_gene_variant		5		ENSP00000476528.1	V9GY92

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29682

AN:

151552

Hom.:

3661

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0491

Gnomad AMI

AF:

0.294

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.229

Gnomad EAS

AF:

0.284

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.242

Gnomad NFE

AF:

0.267

Gnomad OTH

AF:

0.199

GnomAD4 exome

AF:

0.189

AC:

AN:

350

Hom.:

AF XY:

0.165

AC XY:

AN XY:

182

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.100

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.118

AC:

AN:

European-Finnish (FIN)

AF:

0.100

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.219

AC:

AN:

228

Other (OTH)

AF:

0.214

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.196

AC:

29680

AN:

151670

Hom.:

3659

Cov.:

AF XY:

0.196

AC XY:

14494

AN XY:

74104

show subpopulations

African (AFR)

AF:

0.0492

AC:

2038

AN:

41464

American (AMR)

AF:

0.186

AC:

2827

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

795

AN:

3466

East Asian (EAS)

AF:

0.284

AC:

1471

AN:

5176

South Asian (SAS)

AF:

0.182

AC:

872

AN:

4796

European-Finnish (FIN)

AF:

0.272

AC:

2859

AN:

10526

Middle Eastern (MID)

AF:

0.240

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.267

AC:

18067

AN:

67716

Other (OTH)

AF:

0.197

AC:

415

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1149

2298

3448

4597

5746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

318

636

954

1272

1590

<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:

0.222

Hom.:

1677

Bravo

AF:

0.183

Asia WGS

AF:

0.200

AC:

689

AN:

3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.2

(source)

DANN

Benign

0.76

PhyloP100

0.061

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over