rs12314237

Positions:

• chr12-66591446-A-G

Variant summary

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

The NM_001366722.1(GRIP1):​c.136+5401T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 151,904 control chromosomes in the GnomAD database, including 4,858 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 0.25 (4858 hom., cov: 31)
• Consequence: GRIP1 NM_001366722.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373

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 (AMR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIP1	NM_001366722.1	c.136+5401T>C		intron_variant		ENST00000359742.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRIP1	ENST00000359742.9	c.136+5401T>C		intron_variant		5	NM_001366722.1	P1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37899 AN: 151786 Hom.: 4849 Cov.: 31

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.250 AC: 37932 AN: 151904 Hom.: 4858 Cov.: 31 AF XY: 0.250 AC XY: 18535 AN XY: 74244

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.263

Alfa AF: 0.254 Hom.: 2527

Bravo AF: 0.249

Asia WGS AF: 0.225 AC: 787 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	1.5
DANN	Benign	0.32

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: rs12314237; hg19: chr12-66985226;