rs4913307

chr12-66470511-T-C

Variant summary

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

The NM_001366722.1(GRIP1):c.725-5089A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 151,730 control chromosomes in the GnomAD database, including 25,488 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 0.57 (25488 hom., cov: 30)
• Consequence: GRIP1 NM_001366722.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.04

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIP1	NM_001366722.1	c.725-5089A>G		intron_variant		ENST00000359742.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIP1	ENST00000359742.9	c.725-5089A>G		intron_variant		5	NM_001366722.1	P1

Frequencies

GnomAD3 genomes AF: 0.567 AC: 85995 AN: 151612 Hom.: 25476 Cov.: 30

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.567 AC: 86032 AN: 151730 Hom.: 25488 Cov.: 30 AF XY: 0.558 AC XY: 41378 AN XY: 74160

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.720

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.676

Gnomad4 OTH AF: 0.605

Alfa AF: 0.655 Hom.: 68356

Bravo AF: 0.560

Asia WGS AF: 0.417 AC: 1451 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.68
Dann	Benign	0.63

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: rs4913307; hg19: chr12-66864291;