dbSNP rs1038923: GRIP1:c.1199-64A>G (chr12-66455628-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001366722.1(GRIP1):c.1199-64A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 1,460,710 control chromosomes in the GnomAD database, including 306,704 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 0.65 ( 32955 hom., cov: 31)

Exomes 𝑓: 0.64 ( 273749 hom. )

Consequence

GRIP1
NM_001366722.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.212

Publications

5 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIP1	NM_001366722.1 link	c.1199-64A>G		intron_variant	Intron 10 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.1199-64A>G		intron_variant	Intron 10 of 24	5	NM_001366722.1	ENSP00000352780.4		Q9Y3R0-1

Frequencies

GnomAD3 genomes

AF:

0.650

AC:

98789

AN:

151892

Hom.:

32915

Cov.:

show subpopulations

Gnomad AFR

AF:

0.740

Gnomad AMI

AF:

0.666

Gnomad AMR

AF:

0.549

Gnomad ASJ

AF:

0.725

Gnomad EAS

AF:

0.432

Gnomad SAS

AF:

0.510

Gnomad FIN

AF:

0.458

Gnomad MID

AF:

0.785

Gnomad NFE

AF:

0.670

Gnomad OTH

AF:

0.668

GnomAD4 exome

AF:

0.640

AC:

837909

AN:

1308698

Hom.:

273749

AF XY:

0.637

AC XY:

419834

AN XY:

658998

show subpopulations

African (AFR)

AF:

0.749

AC:

22944

AN:

30632

American (AMR)

AF:

0.412

AC:

18173

AN:

44064

Ashkenazi Jewish (ASJ)

AF:

0.734

AC:

18459

AN:

25152

East Asian (EAS)

AF:

0.430

AC:

16724

AN:

38926

South Asian (SAS)

AF:

0.512

AC:

42332

AN:

82716

European-Finnish (FIN)

AF:

0.478

AC:

24896

AN:

52080

Middle Eastern (MID)

AF:

0.700

AC:

2806

AN:

4008

European-Non Finnish (NFE)

AF:

0.672

AC:

656146

AN:

976010

Other (OTH)

AF:

0.643

AC:

35429

AN:

55110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

15294

30588

45881

61175

76469

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15974

31948

47922

63896

79870

<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:

0.650

AC:

98871

AN:

152012

Hom.:

32955

Cov.:

AF XY:

0.637

AC XY:

47342

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.740

AC:

30694

AN:

41472

American (AMR)

AF:

0.548

AC:

8371

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.725

AC:

2514

AN:

3468

East Asian (EAS)

AF:

0.432

AC:

2228

AN:

5152

South Asian (SAS)

AF:

0.510

AC:

2455

AN:

4812

European-Finnish (FIN)

AF:

0.458

AC:

4840

AN:

10568

Middle Eastern (MID)

AF:

0.789

AC:

232

AN:

294

European-Non Finnish (NFE)

AF:

0.670

AC:

45524

AN:

67950

Other (OTH)

AF:

0.667

AC:

1407

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1669

3337

5006

6674

8343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

788

1576

2364

3152

3940

<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:

0.661

Hom.:

19550

Bravo

AF:

0.660

Asia WGS

AF:

0.527

AC:

1836

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

8.6

(source)

DANN

Benign

0.74

PhyloP100

0.21

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

Computational scores

Splicing

Publications

Other links and lift over