15-41835094-G-A

Position:

chr15-41835094-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_001114632.2(JMJD7):c.343G>A(p.Val115Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000395 in 1,613,384 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

JMJD7
NM_001114632.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.53

Variant links:

Genes affected

JMJD7 (HGNC:34397): (jumonji domain containing 7) This gene encodes a highly conserved protein with a JmjC domain, which are part of the cupin metalloenzyme superfamily. JmjC proteins may function as 2-oxoglutarate-Fe(II)-dependent dioxygenases. Most tissues also express read-through transcripts from this gene into the downstream phospholipase A2, group IVB (cytosolic) gene, some of which may encode fusion proteins combining the N-terminus of this protein with the phospholipase A2, group IVB protein. [provided by RefSeq, Jul 2008]

JMJD7 links:

JMJD7-PLA2G4B (HGNC:34449): (JMJD7-PLA2G4B readthrough) This locus represents naturally-occurring readthrough transcription between the neighboring jumonji domain containing 7 (JMJD7) and phospholipase A2, group IVB (cytosolic) (PLA2G4B) genes. Readthrough transcripts encode fusion proteins that share amino acid sequence with each individual gene product, including a partial JmjC domain and downstream C2 and phospholipase A2 domains. Alternatively spliced transcript variants have been observed. [provided by RefSeq, Oct 2013]

JMJD7-PLA2G4B links:

JMJD7-PLA2G4B (HGNC:):

JMJD7-PLA2G4B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008355737).

BP6

Variant 15-41835094-G-A is Benign according to our data. Variant chr15-41835094-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3035070.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JMJD7	NM_001114632.2 linkuse as main transcript	c.343G>A	p.Val115Met	missense_variant	3/8	ENST00000397299.9	NP_001108104.1	P0C870
JMJD7-PLA2G4B	NM_005090.4 linkuse as main transcript	c.343G>A	p.Val115Met	missense_variant	3/25		NP_005081.1	P0C869-6
JMJD7-PLA2G4B	NM_001198588.2 linkuse as main transcript	c.343G>A	p.Val115Met	missense_variant	3/24		NP_001185517.1	P0C869-7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JMJD7	ENST00000397299.9 linkuse as main transcript	c.343G>A	p.Val115Met	missense_variant	3/8	1	NM_001114632.2	ENSP00000380467.4		P0C870
JMJD7-PLA2G4B	ENST00000382448.8 linkuse as main transcript	c.343G>A	p.Val115Met	missense_variant	3/25	2		ENSP00000371886.4

Frequencies

GnomAD3 genomes

AF:

0.00181

AC:

275

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00606

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000669

AC:

166

AN:

248014

Hom.:

AF XY:

0.000528

AC XY:

AN XY:

134344

show subpopulations

Gnomad AFR exome

AF:

0.00684

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.00229

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000722

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000248

AC:

362

AN:

1461074

Hom.:

Cov.:

AF XY:

0.000231

AC XY:

168

AN XY:

726842

show subpopulations

Gnomad4 AFR exome

AF:

0.00603

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000396

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.00181

AC:

275

AN:

152310

Hom.:

Cov.:

AF XY:

0.00193

AC XY:

144

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00604

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000324

Hom.:

Bravo

AF:

0.00184

ESP6500AA

AF:

0.00817

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000684

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

JMJD7-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 22, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0064

T;T;.;.;.

Eigen

Benign

0.18

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.83

T;T;T;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.0084

T;T;T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

1.5

L;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.4

N;N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.13

T;T;T;D;D

Sift4G

Benign

0.30

T;T;T;D;T

Polyphen

0.72

P;.;.;.;.

Vest4

0.43

MVP

0.56

MPC

0.043

ClinPred

0.028

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.42

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over