NM_014619.5:c.636C>T

Variant names:

• chr11-120831976-C-T
• rs148308915
• NM_014619.5:c.636C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_014619.5(GRIK4):​c.636C>T​(p.Thr212Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,613,772 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0011 (1 hom.)
• Consequence: GRIK4 NM_014619.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.31
• Publications: 2 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]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 11-120831976-C-T is Benign according to our data. Variant chr11-120831976-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 720353.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.31 with no splicing effect.
• BS2: High AC in GnomAd4 at 185 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014619.5. 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
	GRIK4	NM_014619.5	MANE Select	c.636C>T	p.Thr212Thr	synonymous	Exon 7 of 21	NP_055434.2
	GRIK4	NM_001282470.3		c.636C>T	p.Thr212Thr	synonymous	Exon 6 of 20	NP_001269399.1	A0A8D9PH79
	GRIK4	NM_001440402.1		c.636C>T	p.Thr212Thr	synonymous	Exon 9 of 23	NP_001427331.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK4	ENST00000527524.8	TSL:2 MANE Select	c.636C>T	p.Thr212Thr	synonymous	Exon 7 of 21	ENSP00000435648.2	Q16099
	GRIK4	ENST00000438375.2	TSL:1	c.636C>T	p.Thr212Thr	synonymous	Exon 6 of 20	ENSP00000404063.2	Q16099
	GRIK4	ENST00000533291.5	TSL:1	n.1034C>T		non_coding_transcript_exon	Exon 7 of 18

Frequencies

GnomAD3 genomes AF: 0.00122 AC: 185 AN: 152118 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00235

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000768 AC: 193 AN: 251374 AF XY: 0.000721

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000277

Gnomad NFE exome AF: 0.00143

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00106 AC: 1549 AN: 1461654 Hom.: 1 Cov.: 32 AF XY: 0.00105 AC XY: 761 AN XY: 727120

African (AFR) AF: 0.000269 AC: 9 AN: 33476

American (AMR) AF: 0.000179 AC: 8 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26132

East Asian (EAS) AF: 0.000302 AC: 12 AN: 39696

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86234

European-Finnish (FIN) AF: 0.000300 AC: 16 AN: 53412

Middle Eastern (MID) AF: 0.00105 AC: 6 AN: 5698

European-Non Finnish (NFE) AF: 0.00128 AC: 1427 AN: 1111908

Other (OTH) AF: 0.00111 AC: 67 AN: 60382

GnomAD4 genome AF: 0.00122 AC: 185 AN: 152118 Hom.: 0 Cov.: 31 AF XY: 0.00109 AC XY: 81 AN XY: 74304

African (AFR) AF: 0.000362 AC: 15 AN: 41420

American (AMR) AF: 0.000131 AC: 2 AN: 15286

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00235 AC: 160 AN: 68024

Other (OTH) AF: 0.000957 AC: 2 AN: 2090

Alfa AF: 0.00138 Hom.: 0

Bravo AF: 0.000778

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00202

EpiControl AF: 0.000948

ClinVar

ClinVar submissions

Significance: Likely 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	-0.73
CADD	Benign	6.0
DANN	Benign	0.90
PhyloP100		-2.3
Mutation Taster		=100/0	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: rs148308915; hg19: chr11-120702685; COSMIC: COSV70803882;