15-41835222-G-T

Variant names:

• chr15-41835222-G-T
• rs75094146
• NM_001114632.2:c.471G>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001114632.2(JMJD7):​c.471G>T​(p.Leu157Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000835 in 1,597,494 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (6 hom., cov: 33)
  • Exomes 𝑓: 0.00046 (3 hom.)
• Consequence: JMJD7 NM_001114632.2 splice_region, synonymous
• Scores: Splicing: ADA: 0.0001044
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.294
• Publications: 2 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: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 15-41835222-G-T is Benign according to our data. Variant chr15-41835222-G-T is described in ClinVar as Benign. ClinVar VariationId is 787425.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.294 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.000464 (671/1445184) while in subpopulation AFR AF = 0.0166 (555/33448). AF 95% confidence interval is 0.0155. There are 3 homozygotes in GnomAdExome4. There are 292 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

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.471G>T	p.Leu157Leu	splice_region synonymous	Exon 3 of 8	NP_001108104.1	P0C870
	JMJD7-PLA2G4B	NM_005090.4		c.471G>T	p.Leu157Leu	splice_region synonymous	Exon 3 of 25	NP_005081.1
	JMJD7-PLA2G4B	NM_001198588.2		c.471G>T	p.Leu157Leu	splice_region synonymous	Exon 3 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.471G>T	p.Leu157Leu	splice_region synonymous	Exon 3 of 8	ENSP00000380467.4	P0C870
	JMJD7-PLA2G4B	ENST00000382448.8	TSL:2	c.471G>T	p.Leu157Leu	splice_region synonymous	Exon 3 of 25	ENSP00000371886.4
	JMJD7-PLA2G4B	ENST00000342159.6	TSL:2	c.471G>T	p.Leu157Leu	splice_region synonymous	Exon 3 of 24	ENSP00000342785.4

Frequencies

GnomAD3 genomes AF: 0.00432 AC: 658 AN: 152192 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

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: 0.000103

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00106 AC: 239 AN: 225134 AF XY: 0.000832

Gnomad AFR exome AF: 0.0144

Gnomad AMR exome AF: 0.000473

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000294

Gnomad OTH exome AF: 0.000874

GnomAD4 exome AF: 0.000464 AC: 671 AN: 1445184 Hom.: 3 Cov.: 31 AF XY: 0.000406 AC XY: 292 AN XY: 719188

African (AFR) AF: 0.0166 AC: 555 AN: 33448

American (AMR) AF: 0.000609 AC: 27 AN: 44368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26024

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 86060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38852

Middle Eastern (MID) AF: 0.000903 AC: 5 AN: 5536

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1111078

Other (OTH) AF: 0.000997 AC: 60 AN: 60170

GnomAD4 genome AF: 0.00435 AC: 663 AN: 152310 Hom.: 6 Cov.: 33 AF XY: 0.00407 AC XY: 303 AN XY: 74500

African (AFR) AF: 0.0149 AC: 620 AN: 41566

American (AMR) AF: 0.00157 AC: 24 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68008

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00184 Hom.: 3

Bravo AF: 0.00500

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.2
DANN	Benign	0.57
PhyloP100		-0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Mutation Taster		=53/47	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00010
dbscSNV1_RF	Benign	0.0
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: rs75094146; hg19: chr15-42127420;