rs2457450

Positions:

• chr10-85623138-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017551.3(GRID1):​c.2194-3105T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 151,870 control chromosomes in the GnomAD database, including 10,014 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 0.36 (10014 hom., cov: 32)
• Consequence: GRID1 NM_017551.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.360

Genes affected

GRID1 (HGNC:4575): (glutamate ionotropic receptor delta type subunit 1) This gene encodes a subunit of glutamate receptor channels. These channels mediate most of the fast excitatory synaptic transmission in the central nervous system and play key roles in synaptic plasticity.[provided by RefSeq, Jan 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRID1	NM_017551.3	c.2194-3105T>G		intron_variant		ENST00000327946.12	NP_060021.1
GRID1	XM_047425122.1	c.907-3105T>G		intron_variant			XP_047281078.1
GRID1	XM_047425123.1	c.907-3105T>G		intron_variant			XP_047281079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRID1	ENST00000327946.12	c.2194-3105T>G		intron_variant		2	NM_017551.3	ENSP00000330148	P1
GRID1	ENST00000464741.2	c.2194-9491T>G		intron_variant, NMD_transcript_variant		1		ENSP00000433064

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54906 AN: 151752 Hom.: 10006 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.362 AC: 54933 AN: 151870 Hom.: 10014 Cov.: 32 AF XY: 0.365 AC XY: 27086 AN XY: 74204

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.375

Alfa AF: 0.365 Hom.: 5084

Bravo AF: 0.365

Asia WGS AF: 0.436 AC: 1514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.9
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs2457450; hg19: chr10-87382895;