rs4393254

Positions:

• chr10-85984641-C-T

Variant summary

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

The NM_017551.3(GRID1):​c.727-68402G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0698 in 152,244 control chromosomes in the GnomAD database, including 424 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 0.070 (424 hom., cov: 32)
• Consequence: GRID1 NM_017551.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRID1	NM_017551.3	c.727-68402G>A		intron_variant		ENST00000327946.12	NP_060021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRID1	ENST00000327946.12	c.727-68402G>A		intron_variant		2	NM_017551.3	ENSP00000330148.7
GRID1	ENST00000464741.2	n.727-68402G>A		intron_variant		1		ENSP00000433064.1

Frequencies

GnomAD3 genomes AF: 0.0698 AC: 10623 AN: 152126 Hom.: 423 Cov.: 32

Gnomad AFR AF: 0.0357

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0611

Gnomad ASJ AF: 0.0639

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0271

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0947

Gnomad OTH AF: 0.0709

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

GnomAD4 genome AF: 0.0698 AC: 10624 AN: 152244 Hom.: 424 Cov.: 32 AF XY: 0.0688 AC XY: 5120 AN XY: 74440

Gnomad4 AFR AF: 0.0357

Gnomad4 AMR AF: 0.0610

Gnomad4 ASJ AF: 0.0639

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0278

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.0947

Gnomad4 OTH AF: 0.0701

Alfa AF: 0.0873 Hom.: 801

Bravo AF: 0.0651

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.47
DANN	Benign	0.69

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: rs4393254; hg19: chr10-87744398; COSMIC: COSV60033622;