12-66576476-T-C

Variant names:

• chr12-66576476-T-C
• rs12581890
• NM_001366722.1:c.136+20371A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

GRIP1 Gene-Disease associations (from GenCC):

• Fraser syndrome 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
• Fraser syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366722.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP1	NM_001366722.1	MANE Select	c.136+20371A>G		intron	N/A	NP_001353651.1	Q9Y3R0-1
	GRIP1	NM_001379345.1		c.214+20371A>G		intron	N/A	NP_001366274.1
	GRIP1	NM_001439322.1		c.139+20371A>G		intron	N/A	NP_001426251.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP1	ENST00000359742.9	TSL:5 MANE Select	c.136+20371A>G		intron	N/A	ENSP00000352780.4	Q9Y3R0-1
	GRIP1	ENST00000398016.7	TSL:1	c.136+20371A>G		intron	N/A	ENSP00000381098.3	Q9Y3R0-3
	GRIP1	ENST00000696989.1		c.361+20371A>G		intron	N/A	ENSP00000513025.1	A0A8V8TLS6

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

African (AFR) AF: 0.391 AC: 16197 AN: 41464

American (AMR) AF: 0.294 AC: 4498 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 807 AN: 3468

East Asian (EAS) AF: 0.216 AC: 1117 AN: 5174

South Asian (SAS) AF: 0.211 AC: 1020 AN: 4826

European-Finnish (FIN) AF: 0.257 AC: 2725 AN: 10584

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17420 AN: 67994

Other (OTH) AF: 0.283 AC: 598 AN: 2114

Alfa AF: 0.203 Hom.: 594

Bravo AF: 0.299

Asia WGS AF: 0.240 AC: 841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.83
DANN	Benign	0.74
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12581890; hg19: chr12-66970256;