chr10-85623138-A-C

Variant names:

• chr10-85623138-A-C
• rs2457450
• NM_017551.3:c.2194-3105T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GRID1	NM_017551.3	c.2194-3105T>G		intron_variant	Intron 13 of 15	ENST00000327946.12	NP_060021.1
GRID1	XM_047425122.1	c.907-3105T>G		intron_variant	Intron 6 of 8		XP_047281078.1
GRID1	XM_047425123.1	c.907-3105T>G		intron_variant	Intron 6 of 8		XP_047281079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRID1	ENST00000327946.12	c.2194-3105T>G		intron_variant	Intron 13 of 15	2	NM_017551.3	ENSP00000330148.7
GRID1	ENST00000464741.2	n.2194-9491T>G		intron_variant	Intron 13 of 14	1		ENSP00000433064.1

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

African (AFR) AF: 0.348 AC: 14405 AN: 41414

American (AMR) AF: 0.400 AC: 6105 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1634 AN: 3468

East Asian (EAS) AF: 0.340 AC: 1749 AN: 5148

South Asian (SAS) AF: 0.486 AC: 2332 AN: 4800

European-Finnish (FIN) AF: 0.311 AC: 3279 AN: 10544

Middle Eastern (MID) AF: 0.524 AC: 153 AN: 292

European-Non Finnish (NFE) AF: 0.356 AC: 24170 AN: 67922

Other (OTH) AF: 0.375 AC: 791 AN: 2108

Alfa AF: 0.366 Hom.: 5619

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
PhyloP100		-0.36
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: rs2457450; hg19: chr10-87382895;