chr15-41834758-C-T

Variant names:

• chr15-41834758-C-T
• rs7174710
• NM_001114632.2:c.83C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001114632.2(JMJD7):​c.83C>T​(p.Ala28Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A28G) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: JMJD7 NM_001114632.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 0 publications found

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: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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06541067).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114632.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD7	NM_001114632.2	MANE Select	c.83C>T	p.Ala28Val	missense	Exon 2 of 8	NP_001108104.1	P0C870
	JMJD7-PLA2G4B	NM_005090.4		c.83C>T	p.Ala28Val	missense	Exon 2 of 25	NP_005081.1
	JMJD7-PLA2G4B	NM_001198588.2		c.83C>T	p.Ala28Val	missense	Exon 2 of 24	NP_001185517.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD7	ENST00000397299.9	TSL:1 MANE Select	c.83C>T	p.Ala28Val	missense	Exon 2 of 8	ENSP00000380467.4	P0C870
	JMJD7-PLA2G4B	ENST00000382448.8	TSL:2	c.83C>T	p.Ala28Val	missense	Exon 2 of 25	ENSP00000371886.4
	JMJD7	ENST00000431823.1	TSL:5	c.-215C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 7	ENSP00000399600.1	C9K0I3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461808 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727190

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111986

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0094	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.5
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.068
Sift	Benign	0.20	T
Sift4G	Benign	0.31	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.28		Loss of phosphorylation at Y31 (P = 0.1826)
MVP		0.16
MPC		0.021
ClinPred		0.040	T
GERP RS		1.3
Varity_R		0.10
gMVP		0.35
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs7174710; hg19: chr15-42126956;