chr12-66576476-T-C

Position:

• chr12-66576476-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.136+20371A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,106 control chromosomes in the GnomAD database, including 6,958 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 0.29 (6958 hom., cov: 33)
• Consequence: GRIP1 NM_001366722.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIP1	NM_001366722.1	c.136+20371A>G		intron_variant		ENST00000359742.9	NP_001353651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIP1	ENST00000359742.9	c.136+20371A>G		intron_variant		5	NM_001366722.1	ENSP00000352780	P1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44623 AN: 151988 Hom.: 6936 Cov.: 33

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.294 AC: 44688 AN: 152106 Hom.: 6958 Cov.: 33 AF XY: 0.293 AC XY: 21772 AN XY: 74376

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.283

Alfa AF: 0.196 Hom.: 536

Bravo AF: 0.299

Asia WGS AF: 0.240 AC: 841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.83
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: rs12581890; hg19: chr12-66970256;