rs10748053

Variant names:

• chr12-66551165-G-A
• rs10748053
• NM_001366722.1:c.137-9215C>T

Variant summary

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

The NM_001366722.1(GRIP1):​c.137-9215C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 152,170 control chromosomes in the GnomAD database, including 40,659 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 0.72 (40659 hom., cov: 34)
• Consequence: GRIP1 NM_001366722.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.232
• 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: 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIP1	NM_001366722.1	c.137-9215C>T		intron_variant	Intron 2 of 24	ENST00000359742.9	NP_001353651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIP1	ENST00000359742.9	c.137-9215C>T		intron_variant	Intron 2 of 24	5	NM_001366722.1	ENSP00000352780.4

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110211 AN: 152052 Hom.: 40604 Cov.: 34

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.725 AC: 110318 AN: 152170 Hom.: 40659 Cov.: 34 AF XY: 0.718 AC XY: 53419 AN XY: 74370

African (AFR) AF: 0.857 AC: 35607 AN: 41550

American (AMR) AF: 0.716 AC: 10935 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 2253 AN: 3472

East Asian (EAS) AF: 0.527 AC: 2724 AN: 5172

South Asian (SAS) AF: 0.629 AC: 3039 AN: 4828

European-Finnish (FIN) AF: 0.578 AC: 6109 AN: 10562

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47286 AN: 67988

Other (OTH) AF: 0.723 AC: 1525 AN: 2110

Alfa AF: 0.703 Hom.: 108972

Bravo AF: 0.737

Asia WGS AF: 0.605 AC: 2106 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	7.0
DANN	Benign	0.58
PhyloP100		0.23
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: rs10748053; hg19: chr12-66944945;