11-120819909-C-G

Variant names:

• chr11-120819909-C-G
• rs41297895
• NM_014619.5:c.500C>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_014619.5(GRIK4):​c.500C>G​(p.Ala167Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00914 in 1,613,830 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0059 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0095 (79 hom.)
• Consequence: GRIK4 NM_014619.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 7.53
• Publications: 9 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011505038).
• BP6: Variant 11-120819909-C-G is Benign according to our data. Variant chr11-120819909-C-G is described in ClinVar as Benign. ClinVar VariationId is 771750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 900 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.500C>G	p.Ala167Gly	missense	Exon 6 of 21	NP_055434.2
	GRIK4	NM_001282470.3		c.500C>G	p.Ala167Gly	missense	Exon 5 of 20	NP_001269399.1	A0A8D9PH79
	GRIK4	NM_001440402.1		c.500C>G	p.Ala167Gly	missense	Exon 8 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.500C>G	p.Ala167Gly	missense	Exon 6 of 21	ENSP00000435648.2	Q16099
	GRIK4	ENST00000438375.2	TSL:1	c.500C>G	p.Ala167Gly	missense	Exon 5 of 20	ENSP00000404063.2	Q16099
	GRIK4	ENST00000533291.5	TSL:1	n.898C>G		non_coding_transcript_exon	Exon 6 of 18

Frequencies

GnomAD3 genomes AF: 0.00592 AC: 901 AN: 152170 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00183

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00664

Gnomad FIN AF: 0.00792

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00941

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00663 AC: 1664 AN: 251158 AF XY: 0.00715

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.00188

Gnomad ASJ exome AF: 0.00398

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00694

Gnomad NFE exome AF: 0.00973

Gnomad OTH exome AF: 0.00539

GnomAD4 exome AF: 0.00948 AC: 13853 AN: 1461542 Hom.: 79 Cov.: 32 AF XY: 0.00953 AC XY: 6929 AN XY: 727066

African (AFR) AF: 0.000777 AC: 26 AN: 33466

American (AMR) AF: 0.00219 AC: 98 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00402 AC: 105 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00830 AC: 716 AN: 86236

European-Finnish (FIN) AF: 0.00792 AC: 423 AN: 53394

Middle Eastern (MID) AF: 0.00641 AC: 36 AN: 5618

European-Non Finnish (NFE) AF: 0.0108 AC: 12009 AN: 1111916

Other (OTH) AF: 0.00729 AC: 440 AN: 60362

GnomAD4 genome AF: 0.00591 AC: 900 AN: 152288 Hom.: 4 Cov.: 32 AF XY: 0.00598 AC XY: 445 AN XY: 74458

African (AFR) AF: 0.00183 AC: 76 AN: 41562

American (AMR) AF: 0.00275 AC: 42 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00664 AC: 32 AN: 4818

European-Finnish (FIN) AF: 0.00792 AC: 84 AN: 10608

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

European-Non Finnish (NFE) AF: 0.00941 AC: 640 AN: 68036

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

Alfa AF: 0.00722 Hom.: 3

Bravo AF: 0.00501

TwinsUK AF: 0.0111 AC: 41

ALSPAC AF: 0.0109 AC: 42

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.0107 AC: 92

ExAC AF: 0.00675 AC: 819

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.00965

EpiControl AF: 0.00759

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	D
MetaRNN	Benign	0.012	T
MetaSVM	Uncertain	0.17	D
MutationAssessor	Benign	2.0	M
PhyloP100		7.5
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.57
Sift	Benign	0.065	T
Sift4G	Uncertain	0.045	D
Polyphen		0.79	P
Vest4		0.75
MVP		0.43
MPC		0.83
ClinPred		0.047	T
GERP RS		4.7
Varity_R		0.28
gMVP		0.75
Mutation Taster		=82/18	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: rs41297895; hg19: chr11-120690618;