12-66510743-T-C

Variant names:

• chr12-66510743-T-C
• rs7956611
• NM_001366722.1:c.724+4876A>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.724+4876A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 151,792 control chromosomes in the GnomAD database, including 7,322 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 0.31 (7322 hom., cov: 32)
• Consequence: GRIP1 NM_001366722.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 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.724+4876A>G		intron	N/A	NP_001353651.1	Q9Y3R0-1
	GRIP1	NM_001379345.1		c.802+4876A>G		intron	N/A	NP_001366274.1
	GRIP1	NM_001439322.1		c.727+4876A>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.724+4876A>G		intron	N/A	ENSP00000352780.4	Q9Y3R0-1
	GRIP1	ENST00000398016.7	TSL:1	c.724+4876A>G		intron	N/A	ENSP00000381098.3	Q9Y3R0-3
	GRIP1	ENST00000536215.5	TSL:1	c.556+4876A>G		intron	N/A	ENSP00000446011.1	F5H4Q7

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46854 AN: 151672 Hom.: 7314 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.309 AC: 46889 AN: 151792 Hom.: 7322 Cov.: 32 AF XY: 0.307 AC XY: 22779 AN XY: 74172

African (AFR) AF: 0.311 AC: 12878 AN: 41390

American (AMR) AF: 0.256 AC: 3899 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1245 AN: 3460

East Asian (EAS) AF: 0.153 AC: 790 AN: 5154

South Asian (SAS) AF: 0.325 AC: 1569 AN: 4822

European-Finnish (FIN) AF: 0.273 AC: 2870 AN: 10528

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22448 AN: 67886

Other (OTH) AF: 0.333 AC: 702 AN: 2106

Alfa AF: 0.329 Hom.: 4206

Bravo AF: 0.305

Asia WGS AF: 0.256 AC: 892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.85
PhyloP100		-0.021
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: rs7956611; hg19: chr12-66904523;