10-86200054-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.520+6310G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 150,332 control chromosomes in the GnomAD database, including 14,001 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 0.42 (14001 hom., cov: 30)
• Consequence: GRID1 NM_017551.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251

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 (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRID1	NM_017551.3	c.520+6310G>A		intron_variant		ENST00000327946.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRID1	ENST00000327946.12	c.520+6310G>A		intron_variant		2	NM_017551.3	P1
GRID1	ENST00000464741.2	c.520+6310G>A		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 62444 AN: 150218 Hom.: 13958 Cov.: 30

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.416 AC: 62551 AN: 150332 Hom.: 14001 Cov.: 30 AF XY: 0.418 AC XY: 30760 AN XY: 73506

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.388

Alfa AF: 0.358 Hom.: 1365

Bravo AF: 0.418

Asia WGS AF: 0.540 AC: 1877 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	5.1
Dann	Benign	0.79

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: rs999383; hg19: chr10-87959811;