rs1038923

Positions:

• chr12-66455628-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001366722.1(GRIP1):​c.1199-64A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 1,460,710 control chromosomes in the GnomAD database, including 306,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.65 (32955 hom., cov: 31)
  • Exomes 𝑓: 0.64 (273749 hom.)
• Consequence: GRIP1 NM_001366722.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 12-66455628-T-C is Benign according to our data. Variant chr12-66455628-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIP1	NM_001366722.1	c.1199-64A>G		intron_variant		ENST00000359742.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIP1	ENST00000359742.9	c.1199-64A>G		intron_variant		5	NM_001366722.1	P1

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98789 AN: 151892 Hom.: 32915 Cov.: 31

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.668

GnomAD4 exome AF: 0.640 AC: 837909 AN: 1308698 Hom.: 273749 AF XY: 0.637 AC XY: 419834 AN XY: 658998

Gnomad4 AFR exome AF: 0.749

Gnomad4 AMR exome AF: 0.412

Gnomad4 ASJ exome AF: 0.734

Gnomad4 EAS exome AF: 0.430

Gnomad4 SAS exome AF: 0.512

Gnomad4 FIN exome AF: 0.478

Gnomad4 NFE exome AF: 0.672

Gnomad4 OTH exome AF: 0.643

GnomAD4 genome AF: 0.650 AC: 98871 AN: 152012 Hom.: 32955 Cov.: 31 AF XY: 0.637 AC XY: 47342 AN XY: 74292

Gnomad4 AFR AF: 0.740

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.725

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.670

Gnomad4 OTH AF: 0.667

Alfa AF: 0.659 Hom.: 17707

Bravo AF: 0.660

Asia WGS AF: 0.527 AC: 1836 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	8.6
DANN	Benign	0.74

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: rs1038923; hg19: chr12-66849408; COSMIC: COSV54027492;