15-41834758-C-G

Position:

• chr15-41834758-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001114632.2(JMJD7):​c.83C>G​(p.Ala28Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0034 in 1,614,138 control chromosomes in the GnomAD database, including 170 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.018 (80 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (90 hom.)
• Consequence: JMJD7 NM_001114632.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.51

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-PLA2G4B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022224784).
• BP6: Variant 15-41834758-C-G is Benign according to our data. Variant chr15-41834758-C-G is described in ClinVar as [Benign]. Clinvar id is 711107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-41834758-C-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JMJD7	NM_001114632.2	c.83C>G	p.Ala28Gly	missense_variant	2/8	ENST00000397299.9
JMJD7-PLA2G4B	NM_005090.4	c.83C>G	p.Ala28Gly	missense_variant	2/25
JMJD7-PLA2G4B	NM_001198588.2	c.83C>G	p.Ala28Gly	missense_variant	2/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JMJD7	ENST00000397299.9	c.83C>G	p.Ala28Gly	missense_variant	2/8	1	NM_001114632.2	P1

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2765 AN: 152214 Hom.: 79 Cov.: 33

Gnomad AFR AF: 0.0642

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00451

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.0139

GnomAD3 exomes AF: 0.00483 AC: 1202 AN: 248812 Hom.: 47 AF XY: 0.00357 AC XY: 481 AN XY: 134662

Gnomad AFR exome AF: 0.0676

Gnomad AMR exome AF: 0.00252

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000630

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00186 AC: 2717 AN: 1461806 Hom.: 90 Cov.: 31 AF XY: 0.00160 AC XY: 1162 AN XY: 727190

Gnomad4 AFR exome AF: 0.0686

Gnomad4 AMR exome AF: 0.00291

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000234

Gnomad4 OTH exome AF: 0.00414

GnomAD4 genome AF: 0.0182 AC: 2773 AN: 152332 Hom.: 80 Cov.: 33 AF XY: 0.0171 AC XY: 1271 AN XY: 74482

Gnomad4 AFR AF: 0.0642

Gnomad4 AMR AF: 0.00451

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.00272 Hom.: 9

Bravo AF: 0.0211

ESP6500AA AF: 0.0611 AC: 269

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00552 AC: 670

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T;.;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.56
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.73	T;T;T
MetaRNN	Benign	0.0022	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;.;.
MutationTaster	Benign	1.0	D;N;N;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.15	T;D;D
Sift4G	Benign	0.26	T;T;T
Polyphen		0.031	B;.;.
Vest4		0.22
MVP		0.26
MPC		0.022
ClinPred		0.0068	T
GERP RS		1.3
Varity_R		0.14
gMVP		0.33

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

Other links and lift over

dbSNP: rs7174710; hg19: chr15-42126956;