rs11176482

Variant names:

• chr12-66902767-T-C
• rs11176482
• NM_001439322.1:c.58+166283A>G

Variant summary

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

The NM_001439322.1(GRIP1):​c.58+166283A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,134 control chromosomes in the GnomAD database, including 5,550 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 0.26 (5550 hom., cov: 33)
• Consequence: GRIP1 NM_001439322.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.643
• 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: Labcorp Genetics (formerly Invitae), G2P, ClinGen
• Fraser syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC124902956 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001439322.1. 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_001439322.1		c.58+166283A>G		intron	N/A	NP_001426251.1
	GRIP1	NM_001439323.1		c.58+166283A>G		intron	N/A	NP_001426252.1
	GRIP1	NM_001379349.1		c.58+166283A>G		intron	N/A	NP_001366278.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP1	ENST00000643019.1		c.58+166283A>G		intron	N/A	ENSP00000495444.1	A0A2R8Y6S7
	GRIP1	ENST00000535721.1	TSL:3	n.114-10813A>G		intron	N/A
	ENSG00000302533	ENST00000787657.1		n.77+4729A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39489 AN: 152016 Hom.: 5533 Cov.: 33

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.260 AC: 39518 AN: 152134 Hom.: 5550 Cov.: 33 AF XY: 0.268 AC XY: 19947 AN XY: 74364

African (AFR) AF: 0.172 AC: 7157 AN: 41508

American (AMR) AF: 0.210 AC: 3205 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 841 AN: 3472

East Asian (EAS) AF: 0.452 AC: 2334 AN: 5166

South Asian (SAS) AF: 0.346 AC: 1668 AN: 4822

European-Finnish (FIN) AF: 0.369 AC: 3900 AN: 10574

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19606 AN: 67996

Other (OTH) AF: 0.235 AC: 498 AN: 2116

Alfa AF: 0.259 Hom.: 1301

Bravo AF: 0.242

Asia WGS AF: 0.354 AC: 1227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.48
PhyloP100		0.64

Splicing

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

Other links and lift over

dbSNP: rs11176482; hg19: chr12-67296547;