NM_001366722.1:c.1199-64A>G

Variant names:

• chr12-66455628-T-C
• rs1038923
• NM_001366722.1:c.1199-64A>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.1199-64A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 1,460,710 control chromosomes in the GnomAD database, including 306,704 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 0.65 (32955 hom., cov: 31)
  • Exomes 𝑓: 0.64 (273749 hom.)
• Consequence: GRIP1 NM_001366722.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.733 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.1199-64A>G		intron	N/A	NP_001353651.1	Q9Y3R0-1
	GRIP1	NM_001379345.1		c.1277-64A>G		intron	N/A	NP_001366274.1
	GRIP1	NM_001439322.1		c.1202-64A>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.1199-64A>G		intron	N/A	ENSP00000352780.4	Q9Y3R0-1
	GRIP1	ENST00000398016.7	TSL:1	c.1043-64A>G		intron	N/A	ENSP00000381098.3	Q9Y3R0-3
	GRIP1	ENST00000536215.5	TSL:1	c.874+7296A>G		intron	N/A	ENSP00000446011.1	F5H4Q7

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98789 AN: 151892 Hom.: 32915 Cov.: 31

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.668

GnomAD4 exome AF: 0.640 AC: 837909 AN: 1308698 Hom.: 273749 AF XY: 0.637 AC XY: 419834 AN XY: 658998

African (AFR) AF: 0.749 AC: 22944 AN: 30632

American (AMR) AF: 0.412 AC: 18173 AN: 44064

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 18459 AN: 25152

East Asian (EAS) AF: 0.430 AC: 16724 AN: 38926

South Asian (SAS) AF: 0.512 AC: 42332 AN: 82716

European-Finnish (FIN) AF: 0.478 AC: 24896 AN: 52080

Middle Eastern (MID) AF: 0.700 AC: 2806 AN: 4008

European-Non Finnish (NFE) AF: 0.672 AC: 656146 AN: 976010

Other (OTH) AF: 0.643 AC: 35429 AN: 55110

GnomAD4 genome AF: 0.650 AC: 98871 AN: 152012 Hom.: 32955 Cov.: 31 AF XY: 0.637 AC XY: 47342 AN XY: 74292

African (AFR) AF: 0.740 AC: 30694 AN: 41472

American (AMR) AF: 0.548 AC: 8371 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 2514 AN: 3468

East Asian (EAS) AF: 0.432 AC: 2228 AN: 5152

South Asian (SAS) AF: 0.510 AC: 2455 AN: 4812

European-Finnish (FIN) AF: 0.458 AC: 4840 AN: 10568

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.670 AC: 45524 AN: 67950

Other (OTH) AF: 0.667 AC: 1407 AN: 2110

Alfa AF: 0.661 Hom.: 19550

Bravo AF: 0.660

Asia WGS AF: 0.527 AC: 1836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.6
DANN	Benign	0.74
PhyloP100		0.21
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: rs1038923; hg19: chr12-66849408; COSMIC: COSV54027492;