rs11176419

Variant names:

• chr12-66767867-T-C
• rs11176419
• NM_001379345.1:c.133+36186A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001379345.1(GRIP1):​c.133+36186A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0813 in 152,234 control chromosomes in the GnomAD database, including 640 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 0.081 (640 hom., cov: 32)
• Consequence: GRIP1 NM_001379345.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276
• Publications: 4 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: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379345.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP1	NM_001379345.1		c.133+36186A>G		intron	N/A	NP_001366274.1
	GRIP1	NM_001439322.1		c.59-170940A>G		intron	N/A	NP_001426251.1
	GRIP1	NM_001439323.1		c.59-170940A>G		intron	N/A	NP_001426252.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP1	ENST00000540433.5	TSL:2	c.-33+36065A>G		intron	N/A	ENSP00000446024.1
	GRIP1	ENST00000541947.1	TSL:5	c.133+36186A>G		intron	N/A	ENSP00000438921.1
	GRIP1	ENST00000539540.5	TSL:5	c.-114+36065A>G		intron	N/A	ENSP00000443392.1

Frequencies

GnomAD3 genomes AF: 0.0812 AC: 12357 AN: 152116 Hom.: 633 Cov.: 32

Gnomad AFR AF: 0.0887

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.0995

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0598

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.0813 AC: 12377 AN: 152234 Hom.: 640 Cov.: 32 AF XY: 0.0812 AC XY: 6047 AN XY: 74438

African (AFR) AF: 0.0888 AC: 3687 AN: 41534

American (AMR) AF: 0.160 AC: 2443 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0995 AC: 345 AN: 3466

East Asian (EAS) AF: 0.118 AC: 612 AN: 5168

South Asian (SAS) AF: 0.147 AC: 707 AN: 4824

European-Finnish (FIN) AF: 0.0106 AC: 113 AN: 10620

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0598 AC: 4069 AN: 68020

Other (OTH) AF: 0.100 AC: 211 AN: 2110

Alfa AF: 0.0730 Hom.: 728

Bravo AF: 0.0952

Asia WGS AF: 0.144 AC: 500 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.37
PhyloP100		0.28

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11176419; hg19: chr12-67161647;