rs4913301

Positions:

• chr12-66462887-G-A
• chr12-66462887-G-T

Variant summary

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

The NM_001366722.1(GRIP1):​c.1042+37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,558,150 control chromosomes in the GnomAD database, including 55,863 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.22 (4349 hom., cov: 31)
  • Exomes 𝑓: 0.27 (51514 hom.)
• Consequence: GRIP1 NM_001366722.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.702

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=-0.82).
• BP6: Variant 12-66462887-G-A is Benign according to our data. Variant chr12-66462887-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIP1	NM_001366722.1	c.1042+37C>T		intron_variant		ENST00000359742.9	NP_001353651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIP1	ENST00000359742.9	c.1042+37C>T		intron_variant		5	NM_001366722.1	ENSP00000352780.4

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33756 AN: 151620 Hom.: 4347 Cov.: 31

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.266

GnomAD3 exomes AF: 0.254 AC: 61753 AN: 243476 Hom.: 8185 AF XY: 0.259 AC XY: 34118 AN XY: 131922

Gnomad AFR exome AF: 0.0996

Gnomad AMR exome AF: 0.222

Gnomad ASJ exome AF: 0.408

Gnomad EAS exome AF: 0.229

Gnomad SAS exome AF: 0.252

Gnomad FIN exome AF: 0.256

Gnomad NFE exome AF: 0.273

Gnomad OTH exome AF: 0.273

GnomAD4 exome AF: 0.267 AC: 375478 AN: 1406424 Hom.: 51514 Cov.: 23 AF XY: 0.268 AC XY: 188413 AN XY: 702462

Gnomad4 AFR exome AF: 0.0942

Gnomad4 AMR exome AF: 0.230

Gnomad4 ASJ exome AF: 0.414

Gnomad4 EAS exome AF: 0.276

Gnomad4 SAS exome AF: 0.258

Gnomad4 FIN exome AF: 0.255

Gnomad4 NFE exome AF: 0.271

Gnomad4 OTH exome AF: 0.267

GnomAD4 genome AF: 0.223 AC: 33762 AN: 151726 Hom.: 4349 Cov.: 31 AF XY: 0.223 AC XY: 16559 AN XY: 74168

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.262

Alfa AF: 0.260 Hom.: 1300

Bravo AF: 0.215

Asia WGS AF: 0.226 AC: 788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.6
DANN	Benign	0.70

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: rs4913301; hg19: chr12-66856667; COSMIC: COSV54048031;