chr12-66528826-C-T

Position:

• chr12-66528826-C-T

Variant summary

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

The NM_001366722.1(GRIP1):​c.502+1005G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 151,876 control chromosomes in the GnomAD database, including 2,682 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 0.17 (2682 hom., cov: 32)
• Consequence: GRIP1 NM_001366722.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112

Genes affected

GRIP1 (HGNC:18708): (glutamate receptor interacting protein 1) This gene encodes a member of the glutamate receptor interacting protein family. The encoded scaffold protein binds to and mediates the trafficking and membrane organization of a number of transmembrane proteins. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIP1	NM_001366722.1	c.502+1005G>A		intron_variant		ENST00000359742.9	NP_001353651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIP1	ENST00000359742.9	c.502+1005G>A		intron_variant		5	NM_001366722.1	ENSP00000352780	P1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26072 AN: 151758 Hom.: 2672 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0796

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.172 AC: 26106 AN: 151876 Hom.: 2682 Cov.: 32 AF XY: 0.168 AC XY: 12486 AN XY: 74226

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.0798

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.140

Alfa AF: 0.143 Hom.: 912

Bravo AF: 0.178

Asia WGS AF: 0.105 AC: 366 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.8
DANN	Benign	0.62

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: rs7971370; hg19: chr12-66922606;