rs4913301

Variant names:

• chr12-66462887-G-A
• rs4913301
• NM_001366722.1:c.1042+37C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-66462887-G-A
• chr12-66462887-G-T

Variant summary

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

The NM_001379345.1(GRIP1):​c.1120+37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,558,150 control chromosomes in the GnomAD database, including 55,863 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 0.22 (4349 hom., cov: 31)
  • Exomes 𝑓: 0.27 (51514 hom.)
• Consequence: GRIP1 NM_001379345.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.702
• Publications: 8 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.271 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP1	NM_001366722.1	MANE Select	c.1042+37C>T		intron	N/A	NP_001353651.1
	GRIP1	NM_001379345.1		c.1120+37C>T		intron	N/A	NP_001366274.1
	GRIP1	NM_001439322.1		c.1045+37C>T		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.1042+37C>T		intron	N/A	ENSP00000352780.4
	GRIP1	ENST00000398016.7	TSL:1	c.1042+37C>T		intron	N/A	ENSP00000381098.3
	GRIP1	ENST00000536215.5	TSL:1	c.874+37C>T		intron	N/A	ENSP00000446011.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33756 AN: 151620 Hom.: 4347 Cov.: 31

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.266

GnomAD2 exomes AF: 0.254 AC: 61753 AN: 243476 AF XY: 0.259

Gnomad AFR exome AF: 0.0996

Gnomad AMR exome AF: 0.222

Gnomad ASJ exome AF: 0.408

Gnomad EAS exome AF: 0.229

Gnomad FIN exome AF: 0.256

Gnomad NFE exome AF: 0.273

Gnomad OTH exome AF: 0.273

GnomAD4 exome AF: 0.267 AC: 375478 AN: 1406424 Hom.: 51514 Cov.: 23 AF XY: 0.268 AC XY: 188413 AN XY: 702462

African (AFR) AF: 0.0942 AC: 3047 AN: 32346

American (AMR) AF: 0.230 AC: 10182 AN: 44224

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 10653 AN: 25708

East Asian (EAS) AF: 0.276 AC: 10830 AN: 39264

South Asian (SAS) AF: 0.258 AC: 21753 AN: 84326

European-Finnish (FIN) AF: 0.255 AC: 13537 AN: 53046

Middle Eastern (MID) AF: 0.342 AC: 1549 AN: 4524

European-Non Finnish (NFE) AF: 0.271 AC: 288366 AN: 1064706

Other (OTH) AF: 0.267 AC: 15561 AN: 58280

GnomAD4 genome AF: 0.223 AC: 33762 AN: 151726 Hom.: 4349 Cov.: 31 AF XY: 0.223 AC XY: 16559 AN XY: 74168

African (AFR) AF: 0.102 AC: 4217 AN: 41398

American (AMR) AF: 0.232 AC: 3527 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1404 AN: 3464

East Asian (EAS) AF: 0.233 AC: 1203 AN: 5156

South Asian (SAS) AF: 0.258 AC: 1240 AN: 4802

European-Finnish (FIN) AF: 0.249 AC: 2608 AN: 10490

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18608 AN: 67878

Other (OTH) AF: 0.262 AC: 552 AN: 2104

Alfa AF: 0.257 Hom.: 2003

Bravo AF: 0.215

Asia WGS AF: 0.226 AC: 788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.6
DANN	Benign	0.70
PhyloP100		0.70
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: rs4913301; hg19: chr12-66856667; COSMIC: COSV54048031;