rs10506502

Variant names:

• chr12-66831749-C-T
• rs10506502
• NM_001439322.1:c.59-234822G>A

Variant summary

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

The NM_001439322.1(GRIP1):​c.59-234822G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,032 control chromosomes in the GnomAD database, including 2,140 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 0.16 (2140 hom., cov: 32)
• Consequence: GRIP1 NM_001439322.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.36 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.59-234822G>A		intron	N/A	NP_001426251.1
	GRIP1	NM_001439323.1		c.59-234822G>A		intron	N/A	NP_001426252.1
	GRIP1	NM_001379349.1		c.59-234822G>A		intron	N/A	NP_001366278.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIP1	ENST00000643019.1		c.59-234822G>A		intron	N/A	ENSP00000495444.1	A0A2R8Y6S7

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24584 AN: 151914 Hom.: 2135 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.162 AC: 24594 AN: 152032 Hom.: 2140 Cov.: 32 AF XY: 0.163 AC XY: 12143 AN XY: 74306

African (AFR) AF: 0.136 AC: 5657 AN: 41470

American (AMR) AF: 0.167 AC: 2550 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 763 AN: 3470

East Asian (EAS) AF: 0.374 AC: 1924 AN: 5146

South Asian (SAS) AF: 0.280 AC: 1347 AN: 4804

European-Finnish (FIN) AF: 0.151 AC: 1593 AN: 10564

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10107 AN: 67974

Other (OTH) AF: 0.191 AC: 403 AN: 2112

Alfa AF: 0.147 Hom.: 273

Bravo AF: 0.162

Asia WGS AF: 0.310 AC: 1076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.080
DANN	Benign	0.64
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs10506502; hg19: chr12-67225529;