11-120815415-C-G

Variant names:

• chr11-120815415-C-G
• rs36083836
• NM_014619.5:c.285C>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_014619.5(GRIK4):​c.285C>G​(p.Leu95Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,552,238 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (31 hom., cov: 33)
  • Exomes 𝑓: 0.00098 (20 hom.)
• Consequence: GRIK4 NM_014619.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.48
• Publications: 1 publications found

Genes affected

GRIK4 (HGNC:4582): (glutamate ionotropic receptor kainate type subunit 4) This gene encodes a protein that belongs to the glutamate-gated ionic channel family. Glutamate functions as the major excitatory neurotransmitter in the central nervous system through activation of ligand-gated ion channels and G protein-coupled membrane receptors. The protein encoded by this gene forms functional heteromeric kainate-preferring ionic channels with the subunits encoded by related gene family members. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

ENSG00000306735 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 11-120815415-C-G is Benign according to our data. Variant chr11-120815415-C-G is described in ClinVar as [Benign]. Clinvar id is 716428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.48 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0101 (1535/152340) while in subpopulation AFR AF = 0.0355 (1474/41578). AF 95% confidence interval is 0.0339. There are 31 homozygotes in GnomAd4. There are 700 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1535 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK4	NM_014619.5	c.285C>G	p.Leu95Leu	synonymous_variant	Exon 5 of 21	ENST00000527524.8	NP_055434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK4	ENST00000527524.8	c.285C>G	p.Leu95Leu	synonymous_variant	Exon 5 of 21	2	NM_014619.5	ENSP00000435648.2

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1531 AN: 152222 Hom.: 32 Cov.: 33

Gnomad AFR AF: 0.0354

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00231 AC: 368 AN: 159368 AF XY: 0.00171

Gnomad AFR exome AF: 0.0341

Gnomad AMR exome AF: 0.00150

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000128

Gnomad OTH exome AF: 0.00159

GnomAD4 exome AF: 0.000979 AC: 1370 AN: 1399898 Hom.: 20 Cov.: 29 AF XY: 0.000845 AC XY: 584 AN XY: 690738

African (AFR) AF: 0.0358 AC: 1136 AN: 31742

American (AMR) AF: 0.00159 AC: 57 AN: 35950

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25144

East Asian (EAS) AF: 0.00 AC: 0 AN: 35962

South Asian (SAS) AF: 0.000139 AC: 11 AN: 78968

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49416

Middle Eastern (MID) AF: 0.00125 AC: 7 AN: 5590

European-Non Finnish (NFE) AF: 0.0000352 AC: 38 AN: 1079052

Other (OTH) AF: 0.00208 AC: 121 AN: 58074

GnomAD4 genome AF: 0.0101 AC: 1535 AN: 152340 Hom.: 31 Cov.: 33 AF XY: 0.00940 AC XY: 700 AN XY: 74486

African (AFR) AF: 0.0355 AC: 1474 AN: 41578

American (AMR) AF: 0.00235 AC: 36 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68038

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.000494 Hom.: 0

Bravo AF: 0.0116

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	4.3
DANN	Benign	0.72
PhyloP100		1.5
Mutation Taster		=98/2	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: rs36083836; hg19: chr11-120686124;