rs7397862

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1838+13G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 1,429,348 control chromosomes in the GnomAD database, including 253,695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 21439 hom., cov: 31)

Exomes 𝑓: 0.60 ( 232256 hom. )

Consequence

GRIP1
NM_001366722.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.268

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 12-66420707-C-A is Benign according to our data. Variant chr12-66420707-C-A is described in ClinVar as Benign. ClinVar VariationId is 261409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIP1	NM_001366722.1 link	c.1838+13G>T		intron_variant	Intron 15 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.1838+13G>T		intron_variant	Intron 15 of 24	5	NM_001366722.1	ENSP00000352780.4		Q9Y3R0-1

Frequencies

GnomAD3 genomes

AF:

0.503

AC:

76414

AN:

151842

Hom.:

21430

Cov.:

show subpopulations

Gnomad AFR

AF:

0.250

Gnomad AMI

AF:

0.732

Gnomad AMR

AF:

0.508

Gnomad ASJ

AF:

0.615

Gnomad EAS

AF:

0.328

Gnomad SAS

AF:

0.560

Gnomad FIN

AF:

0.652

Gnomad MID

AF:

0.554

Gnomad NFE

AF:

0.632

Gnomad OTH

AF:

0.534

GnomAD2 exomes

AF:

0.565

AC:

140688

AN:

249078

AF XY:

0.574

show subpopulations

Gnomad AFR exome

AF:

0.245

Gnomad AMR exome

AF:

0.528

Gnomad ASJ exome

AF:

0.620

Gnomad EAS exome

AF:

0.349

Gnomad FIN exome

AF:

0.647

Gnomad NFE exome

AF:

0.630

Gnomad OTH exome

AF:

0.576

GnomAD4 exome

AF:

0.596

AC:

761429

AN:

1277388

Hom.:

232256

Cov.:

AF XY:

0.598

AC XY:

385800

AN XY:

645368

show subpopulations

African (AFR)

AF:

0.237

AC:

7245

AN:

30566

American (AMR)

AF:

0.530

AC:

23538

AN:

44418

Ashkenazi Jewish (ASJ)

AF:

0.617

AC:

15400

AN:

24966

East Asian (EAS)

AF:

0.317

AC:

12358

AN:

38942

South Asian (SAS)

AF:

0.573

AC:

47281

AN:

82576

European-Finnish (FIN)

AF:

0.651

AC:

34616

AN:

53182

Middle Eastern (MID)

AF:

0.564

AC:

3074

AN:

5450

European-Non Finnish (NFE)

AF:

0.622

AC:

586934

AN:

943004

Other (OTH)

AF:

0.571

AC:

30983

AN:

54284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

12589

25178

37766

50355

62944

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14354

28708

43062

57416

71770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.503

AC:

76453

AN:

151960

Hom.:

21439

Cov.:

AF XY:

0.504

AC XY:

37437

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.251

AC:

10380

AN:

41434

American (AMR)

AF:

0.508

AC:

7754

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.615

AC:

2135

AN:

3470

East Asian (EAS)

AF:

0.328

AC:

1691

AN:

5152

South Asian (SAS)

AF:

0.560

AC:

2695

AN:

4816

European-Finnish (FIN)

AF:

0.652

AC:

6872

AN:

10542

Middle Eastern (MID)

AF:

0.561

AC:

165

AN:

294

European-Non Finnish (NFE)

AF:

0.632

AC:

42960

AN:

67960

Other (OTH)

AF:

0.535

AC:

1133

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1761

3523

5284

7046

8807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

676

1352

2028

2704

3380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.570

Hom.:

5285

Bravo

AF:

0.479

Asia WGS

AF:

0.435

AC:

1514

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Fraser syndrome 1

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

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 12, 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

2.9

(source)

DANN

Benign

0.26

PhyloP100

-0.27

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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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