Genetic Variant GRIP1:c.*1261delA (chr12-66347757-AT-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001366722.1(GRIP1):c.*1261delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.46 ( 16051 hom., cov: 0)

Failed GnomAD Quality Control

Consequence

GRIP1
NM_001366722.1 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.240

Publications

1 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: Labcorp Genetics (formerly Invitae), G2P, ClinGen
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 -10 ACMG points.

BP6

Variant 12-66347757-AT-A is Benign according to our data. Variant chr12-66347757-AT-A is described in ClinVar as Benign. ClinVar VariationId is 310277.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366722.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GRIP1	NM_001366722.1	MANE Select	c.*1261delA	3_prime_UTR	Exon 25 of 25	NP_001353651.1	Q9Y3R0-1
GRIP1	NM_001379345.1		c.*1261delA	3_prime_UTR	Exon 25 of 25	NP_001366274.1
GRIP1	NM_001439322.1		c.*1261delA	3_prime_UTR	Exon 24 of 24	NP_001426251.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GRIP1	ENST00000359742.9	TSL:5 MANE Select	c.*1261delA	3_prime_UTR	Exon 25 of 25	ENSP00000352780.4	Q9Y3R0-1
GRIP1	ENST00000398016.7	TSL:1	c.*1261delA	3_prime_UTR	Exon 24 of 24	ENSP00000381098.3	Q9Y3R0-3
GRIP1	ENST00000696989.1		c.*1261delA	3_prime_UTR	Exon 23 of 23	ENSP00000513025.1	A0A8V8TLS6

Frequencies

GnomAD3 genomes

AF:

0.456

AC:

68843

AN:

151126

Hom.:

16041

Cov.:

show subpopulations

Gnomad AFR

AF:

0.404

Gnomad AMI

AF:

0.370

Gnomad AMR

AF:

0.550

Gnomad ASJ

AF:

0.352

Gnomad EAS

AF:

0.572

Gnomad SAS

AF:

0.477

Gnomad FIN

AF:

0.592

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.442

Gnomad OTH

AF:

0.434

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.456

AC:

68893

AN:

151246

Hom.:

16051

Cov.:

AF XY:

0.463

AC XY:

34211

AN XY:

73858

show subpopulations

African (AFR)

AF:

0.404

AC:

16641

AN:

41210

American (AMR)

AF:

0.550

AC:

8373

AN:

15212

Ashkenazi Jewish (ASJ)

AF:

0.352

AC:

1219

AN:

3462

East Asian (EAS)

AF:

0.574

AC:

2948

AN:

5140

South Asian (SAS)

AF:

0.476

AC:

2287

AN:

4806

European-Finnish (FIN)

AF:

0.592

AC:

6170

AN:

10430

Middle Eastern (MID)

AF:

0.370

AC:

108

AN:

292

European-Non Finnish (NFE)

AF:

0.442

AC:

29902

AN:

67696

Other (OTH)

AF:

0.435

AC:

910

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1860

3720

5579

7439

9299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<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:

0.272

Hom.:

504

Bravo

AF:

0.466

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Fraser syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.24

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over