rs4913307

Variant names:

• chr12-66470511-T-C
• rs4913307
• NM_001366722.1:c.725-5089A>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.725-5089A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 151,730 control chromosomes in the GnomAD database, including 25,488 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 0.57 (25488 hom., cov: 30)
• Consequence: GRIP1 NM_001366722.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.04
• Publications: 10 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.671 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP1	NM_001366722.1	MANE Select	c.725-5089A>G		intron	N/A	NP_001353651.1
	GRIP1	NM_001379345.1		c.803-5089A>G		intron	N/A	NP_001366274.1
	GRIP1	NM_001439322.1		c.728-5089A>G		intron	N/A	NP_001426251.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP1	ENST00000359742.9	TSL:5 MANE Select	c.725-5089A>G		intron	N/A	ENSP00000352780.4
	GRIP1	ENST00000398016.7	TSL:1	c.725-5089A>G		intron	N/A	ENSP00000381098.3
	GRIP1	ENST00000536215.5	TSL:1	c.557-5089A>G		intron	N/A	ENSP00000446011.1

Frequencies

GnomAD3 genomes AF: 0.567 AC: 85995 AN: 151612 Hom.: 25476 Cov.: 30

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.567 AC: 86032 AN: 151730 Hom.: 25488 Cov.: 30 AF XY: 0.558 AC XY: 41378 AN XY: 74160

African (AFR) AF: 0.438 AC: 18115 AN: 41332

American (AMR) AF: 0.529 AC: 8064 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 2501 AN: 3472

East Asian (EAS) AF: 0.316 AC: 1625 AN: 5148

South Asian (SAS) AF: 0.457 AC: 2196 AN: 4804

European-Finnish (FIN) AF: 0.527 AC: 5526 AN: 10482

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.676 AC: 45912 AN: 67918

Other (OTH) AF: 0.605 AC: 1277 AN: 2112

Alfa AF: 0.642 Hom.: 135995

Bravo AF: 0.560

Asia WGS AF: 0.417 AC: 1451 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.68
DANN	Benign	0.63
PhyloP100		-4.0
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: rs4913307; hg19: chr12-66864291;