rs10749535

Positions:

• chr10-86344769-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.235+19172G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,154 control chromosomes in the GnomAD database, including 10,447 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 0.33 (10447 hom., cov: 33)
• Consequence: GRID1 NM_017551.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRID1	NM_017551.3	c.235+19172G>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.235+19172G>A		intron_variant		2	NM_017551.3	ENSP00000330148	P1
GRID1	ENST00000464741.2	c.235+19172G>A		intron_variant, NMD_transcript_variant		1		ENSP00000433064

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50266 AN: 152034 Hom.: 10444 Cov.: 33

Gnomad AFR AF: 0.0824

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.330 AC: 50271 AN: 152154 Hom.: 10447 Cov.: 33 AF XY: 0.332 AC XY: 24710 AN XY: 74384

Gnomad4 AFR AF: 0.0821

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.356

Alfa AF: 0.415 Hom.: 16729

Bravo AF: 0.326

Asia WGS AF: 0.238 AC: 829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.25

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: rs10749535; hg19: chr10-88104526;