chr19-42016956-T-G

Variant names:

• chr19-42016956-T-G
• rs8099939
• NM_002088.5:c.1871+4345A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002088.5(GRIK5):​c.1871+4345A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 151,788 control chromosomes in the GnomAD database, including 16,057 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (16057 hom., cov: 30)
• Consequence: GRIK5 NM_002088.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243
• Publications: 15 publications found

Genes affected

GRIK5 (HGNC:4583): (glutamate ionotropic receptor kainate type subunit 5) 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002088.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK5	NM_002088.5	MANE Select	c.1871+4345A>C		intron	N/A	NP_002079.3
	GRIK5	NM_001301030.2		c.1871+4345A>C		intron	N/A	NP_001287959.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIK5	ENST00000593562.6	TSL:5 MANE Select	c.1871+4345A>C		intron	N/A	ENSP00000470251.1
	GRIK5	ENST00000301218.8	TSL:1	c.1871+4345A>C		intron	N/A	ENSP00000301218.3
	GRIK5	ENST00000262895.7	TSL:1	c.1871+4345A>C		intron	N/A	ENSP00000262895.2

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62651 AN: 151670 Hom.: 16065 Cov.: 30

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.415

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.413 AC: 62640 AN: 151788 Hom.: 16057 Cov.: 30 AF XY: 0.415 AC XY: 30753 AN XY: 74164

African (AFR) AF: 0.109 AC: 4531 AN: 41434

American (AMR) AF: 0.371 AC: 5662 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1517 AN: 3468

East Asian (EAS) AF: 0.565 AC: 2904 AN: 5140

South Asian (SAS) AF: 0.316 AC: 1519 AN: 4802

European-Finnish (FIN) AF: 0.658 AC: 6912 AN: 10500

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.561 AC: 38087 AN: 67890

Other (OTH) AF: 0.416 AC: 874 AN: 2102

Alfa AF: 0.496 Hom.: 53503

Bravo AF: 0.380

Asia WGS AF: 0.368 AC: 1282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.64
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

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: rs8099939; hg19: chr19-42521108;