rs2217223

Variant names:

• chr10-86351873-A-G
• rs2217223
• NM_017551.3:c.235+12068T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017551.3(GRID1):​c.235+12068T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 152,186 control chromosomes in the GnomAD database, including 38,369 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 0.71 (38369 hom., cov: 34)
• Consequence: GRID1 NM_017551.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.740
• Publications: 2 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRID1	NM_017551.3	c.235+12068T>C		intron_variant	Intron 2 of 15	ENST00000327946.12	NP_060021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRID1	ENST00000327946.12	c.235+12068T>C		intron_variant	Intron 2 of 15	2	NM_017551.3	ENSP00000330148.7
GRID1	ENST00000464741.2	n.235+12068T>C		intron_variant	Intron 2 of 14	1		ENSP00000433064.1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107235 AN: 152068 Hom.: 38327 Cov.: 34

Gnomad AFR AF: 0.814

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.707

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

GnomAD4 genome AF: 0.705 AC: 107333 AN: 152186 Hom.: 38369 Cov.: 34 AF XY: 0.704 AC XY: 52356 AN XY: 74390

African (AFR) AF: 0.814 AC: 33811 AN: 41522

American (AMR) AF: 0.712 AC: 10894 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2040 AN: 3470

East Asian (EAS) AF: 0.773 AC: 4009 AN: 5184

South Asian (SAS) AF: 0.498 AC: 2404 AN: 4824

European-Finnish (FIN) AF: 0.689 AC: 7297 AN: 10590

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.656 AC: 44594 AN: 67984

Other (OTH) AF: 0.709 AC: 1496 AN: 2110

Alfa AF: 0.653 Hom.: 16940

Bravo AF: 0.716

Asia WGS AF: 0.662 AC: 2303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.20
DANN	Benign	0.47
PhyloP100		-0.74
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: rs2217223; hg19: chr10-88111630;