rs12371626

Variant names:

• chr12-66422721-C-T
• rs12371626
• NM_001366722.1:c.1769-1932G>A

Variant summary

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

The NM_001366722.1(GRIP1):​c.1769-1932G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,202 control chromosomes in the GnomAD database, including 1,076 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 0.11 (1076 hom., cov: 32)
• Consequence: GRIP1 NM_001366722.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323
• Publications: 6 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 = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIP1	NM_001366722.1	c.1769-1932G>A		intron_variant	Intron 14 of 24	ENST00000359742.9	NP_001353651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIP1	ENST00000359742.9	c.1769-1932G>A		intron_variant	Intron 14 of 24	5	NM_001366722.1	ENSP00000352780.4

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16879 AN: 152084 Hom.: 1070 Cov.: 32

Gnomad AFR AF: 0.0948

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0975

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0623

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.111 AC: 16903 AN: 152202 Hom.: 1076 Cov.: 32 AF XY: 0.108 AC XY: 8023 AN XY: 74408

African (AFR) AF: 0.0950 AC: 3945 AN: 41538

American (AMR) AF: 0.0974 AC: 1488 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 495 AN: 3472

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5184

South Asian (SAS) AF: 0.117 AC: 564 AN: 4812

European-Finnish (FIN) AF: 0.0623 AC: 660 AN: 10600

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9325 AN: 67996

Other (OTH) AF: 0.123 AC: 260 AN: 2110

Alfa AF: 0.129 Hom.: 2737

Bravo AF: 0.114

Asia WGS AF: 0.0720 AC: 248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.38
PhyloP100		-0.32
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: rs12371626; hg19: chr12-66816501;