rs13277

Positions:

chr12-66392311-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001366722.1(GRIP1):c.2461C>G(p.Gln821Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.972 in 1,587,370 control chromosomes in the GnomAD database, including 755,875 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.88 ( 61226 hom., cov: 32)

Exomes 𝑓: 0.98 ( 694649 hom. )

Consequence

GRIP1
NM_001366722.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 7.63

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.574098E-7).

BP6

Variant 12-66392311-G-C is Benign according to our data. Variant chr12-66392311-G-C is described in ClinVar as [Benign]. Clinvar id is 261410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-66392311-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIP1	NM_001366722.1 linkuse as main transcript	c.2461C>G	p.Gln821Glu	missense_variant	19/25	ENST00000359742.9	NP_001353651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIP1	ENST00000359742.9 linkuse as main transcript	c.2461C>G	p.Gln821Glu	missense_variant	19/25	5	NM_001366722.1	ENSP00000352780	P1	Q9Y3R0-1

Frequencies

GnomAD3 genomes

AF:

0.883

AC:

134343

AN:

152090

Hom.:

61211

Cov.:

show subpopulations

Gnomad AFR

AF:

0.636

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.870

Gnomad ASJ

AF:

0.995

Gnomad EAS

AF:

0.937

Gnomad SAS

AF:

0.990

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.975

Gnomad NFE

AF:

0.998

Gnomad OTH

AF:

0.914

GnomAD3 exomes

AF:

0.951

AC:

237058

AN:

249228

Hom.:

114010

AF XY:

0.962

AC XY:

130121

AN XY:

135230

show subpopulations

Gnomad AFR exome

AF:

0.626

Gnomad AMR exome

AF:

0.861

Gnomad ASJ exome

AF:

0.995

Gnomad EAS exome

AF:

0.949

Gnomad SAS exome

AF:

0.993

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.998

Gnomad OTH exome

AF:

0.969

GnomAD4 exome

AF:

0.982

AC:

1409044

AN:

1435162

Hom.:

694649

Cov.:

AF XY:

0.984

AC XY:

704320

AN XY:

715744

show subpopulations

Gnomad4 AFR exome

AF:

0.628

Gnomad4 AMR exome

AF:

0.864

Gnomad4 ASJ exome

AF:

0.995

Gnomad4 EAS exome

AF:

0.901

Gnomad4 SAS exome

AF:

0.993

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.999

Gnomad4 OTH exome

AF:

0.967

GnomAD4 genome

AF:

0.883

AC:

134402

AN:

152208

Hom.:

61226

Cov.:

AF XY:

0.885

AC XY:

65872

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.636

Gnomad4 AMR

AF:

0.870

Gnomad4 ASJ

AF:

0.995

Gnomad4 EAS

AF:

0.937

Gnomad4 SAS

AF:

0.990

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.998

Gnomad4 OTH

AF:

0.915

Alfa

AF:

0.980

Hom.:

55370

Bravo

AF:

0.862

TwinsUK

AF:

0.999

AC:

3706

ALSPAC

AF:

0.999

AC:

3851

ESP6500AA

AF:

0.669

AC:

2717

ESP6500EA

AF:

0.997

AC:

8312

ExAC

AF:

0.949

AC:

114719

Asia WGS

AF:

0.940

AC:

3270

AN:

3478

EpiCase

AF:

0.997

EpiControl

AF:

0.998

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 25, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Fraser syndrome 1

Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 2014	- -

Fraser syndrome 3

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.35

.;T;T;T;.

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.70

T;T;T;T;T

MetaRNN

Benign

8.6e-7

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

.;M;.;.;.

MutationTaster

Benign

0.0000017

P;P;P

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.1

N;N;N;N;N

REVEL

Uncertain

0.36

Sift

Benign

0.33

T;T;T;T;T

Sift4G

Benign

1.0

T;T;.;T;.

Polyphen

0.49

P;P;P;.;.

Vest4

0.28

MPC

0.32

ClinPred

0.056

GERP RS

4.5

Varity_R

0.13

gMVP

0.41

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over