12-66517991-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001366722.1(GRIP1):c.503-15C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,454,456 control chromosomes in the GnomAD database, including 50,228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5667 hom., cov: 32)

Exomes 𝑓: 0.26 ( 44561 hom. )

Consequence

GRIP1
NM_001366722.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.118

Publications

10 publications found

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 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

GRIP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 12-66517991-G-T is Benign according to our data. Variant chr12-66517991-G-T is described in ClinVar as [Benign]. Clinvar id is 261412.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIP1	NM_001366722.1 link	c.503-15C>A		intron_variant	Intron 5 of 24	ENST00000359742.9	NP_001353651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIP1	ENST00000359742.9 link	c.503-15C>A		intron_variant	Intron 5 of 24	5	NM_001366722.1	ENSP00000352780.4		Q9Y3R0-1

Frequencies

GnomAD3 genomes

AF:

0.269

AC:

40835

AN:

151744

Hom.:

5662

Cov.:

show subpopulations

Gnomad AFR

AF:

0.311

Gnomad AMI

AF:

0.316

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.292

Gnomad EAS

AF:

0.149

Gnomad SAS

AF:

0.248

Gnomad FIN

AF:

0.203

Gnomad MID

AF:

0.350

Gnomad NFE

AF:

0.272

Gnomad OTH

AF:

0.284

GnomAD2 exomes

AF:

0.240

AC:

59827

AN:

248892

AF XY:

0.247

show subpopulations

Gnomad AFR exome

AF:

0.314

Gnomad AMR exome

AF:

0.138

Gnomad ASJ exome

AF:

0.296

Gnomad EAS exome

AF:

0.157

Gnomad FIN exome

AF:

0.199

Gnomad NFE exome

AF:

0.270

Gnomad OTH exome

AF:

0.273

GnomAD4 exome

AF:

0.258

AC:

335570

AN:

1302594

Hom.:

44561

Cov.:

AF XY:

0.259

AC XY:

170298

AN XY:

656872

show subpopulations

African (AFR)

AF:

0.309

AC:

9407

AN:

30452

American (AMR)

AF:

0.147

AC:

6538

AN:

44500

Ashkenazi Jewish (ASJ)

AF:

0.294

AC:

7395

AN:

25134

East Asian (EAS)

AF:

0.130

AC:

5070

AN:

38952

South Asian (SAS)

AF:

0.264

AC:

21972

AN:

83072

European-Finnish (FIN)

AF:

0.202

AC:

10729

AN:

53080

Middle Eastern (MID)

AF:

0.285

AC:

1558

AN:

5468

European-Non Finnish (NFE)

AF:

0.267

AC:

258239

AN:

966892

Other (OTH)

AF:

0.266

AC:

14662

AN:

55044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

11113

22227

33340

44454

55567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.269

AC:

40866

AN:

151862

Hom.:

5667

Cov.:

AF XY:

0.266

AC XY:

19753

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.311

AC:

12871

AN:

41398

American (AMR)

AF:

0.225

AC:

3427

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

1010

AN:

3464

East Asian (EAS)

AF:

0.149

AC:

769

AN:

5160

South Asian (SAS)

AF:

0.249

AC:

1193

AN:

4800

European-Finnish (FIN)

AF:

0.203

AC:

2144

AN:

10556

Middle Eastern (MID)

AF:

0.332

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.272

AC:

18456

AN:

67918

Other (OTH)

AF:

0.290

AC:

611

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1499

2997

4496

5994

7493

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.271

Hom.:

18104

Bravo

AF:

0.269

Asia WGS

AF:

0.229

AC:

799

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 15, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Fraser syndrome 1

Benign:2

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Fraser syndrome 3

Benign:2

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.9

(source)

DANN

Benign

0.49

PhyloP100

0.12

PromoterAI

-0.022

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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12-66517991-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over