Variant 6-75922106-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001563.4(IMPG1):c.2377G>A(p.Asp793Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 1,347,536 control chromosomes in the GnomAD database, including 494 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 90 hom., cov: 32)

Exomes 𝑓: 0.014 ( 404 hom. )

Consequence

IMPG1
NM_001563.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.96

Variant links:

Genes affected

IMPG1 (HGNC:6055): (interphotoreceptor matrix proteoglycan 1) This gene encodes a protein that is a major component of the retinal interphotoreceptor matrix. The encoded protein is a proteoglycan that is thought to play a role in maintaining viability of photoreceptor cells and in adhesion of the neural retina to the retinal pigment epithelium. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

IMPG1 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=0.0015089214).

BP6

Variant 6-75922106-C-T is Benign according to our data. Variant chr6-75922106-C-T is described in ClinVar as [Benign]. Clinvar id is 1166320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IMPG1	NM_001563.4 linkuse as main transcript	c.2377G>A	p.Asp793Asn	missense_variant	17/17	ENST00000369950.8
IMPG1	NM_001282368.2 linkuse as main transcript	c.2143G>A	p.Asp715Asn	missense_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IMPG1	ENST00000369950.8 linkuse as main transcript	c.2377G>A	p.Asp793Asn	missense_variant	17/17	1	NM_001563.4	P2	Q17R60-1
IMPG1	ENST00000611179.4 linkuse as main transcript	c.2143G>A	p.Asp715Asn	missense_variant	16/16	5		A2
IMPG1	ENST00000369952.3 linkuse as main transcript	c.460G>A	p.Asp154Asn	missense_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.0188

AC:

2864

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00370

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0537

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.0234

Gnomad FIN

AF:

0.0180

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.0272

AC:

5578

AN:

205146

Hom.:

218

AF XY:

0.0254

AC XY:

2778

AN XY:

109522

show subpopulations

Gnomad AFR exome

AF:

0.00225

Gnomad AMR exome

AF:

0.0545

Gnomad ASJ exome

AF:

0.0151

Gnomad EAS exome

AF:

0.137

Gnomad SAS exome

AF:

0.0154

Gnomad FIN exome

AF:

0.0194

Gnomad NFE exome

AF:

0.00893

Gnomad OTH exome

AF:

0.0237

GnomAD4 exome

AF:

0.0140

AC:

16734

AN:

1195326

Hom.:

404

Cov.:

AF XY:

0.0140

AC XY:

8477

AN XY:

603542

show subpopulations

Gnomad4 AFR exome

AF:

0.00186

Gnomad4 AMR exome

AF:

0.0542

Gnomad4 ASJ exome

AF:

0.0148

Gnomad4 EAS exome

AF:

0.120

Gnomad4 SAS exome

AF:

0.0158

Gnomad4 FIN exome

AF:

0.0179

Gnomad4 NFE exome

AF:

0.00767

Gnomad4 OTH exome

AF:

0.0152

GnomAD4 genome

AF:

0.0188

AC:

2867

AN:

152210

Hom.:

Cov.:

AF XY:

0.0200

AC XY:

1492

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00369

Gnomad4 AMR

AF:

0.0535

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.139

Gnomad4 SAS

AF:

0.0240

Gnomad4 FIN

AF:

0.0180

Gnomad4 NFE

AF:

0.0114

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.0156

Hom.:

Bravo

AF:

0.0215

TwinsUK

AF:

0.0108

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.00274

AC:

ESP6500EA

AF:

0.00768

AC:

ExAC

AF:

0.0179

AC:

2158

Asia WGS

AF:

0.0640

AC:

220

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 29, 2021	- -

Retinal dystrophy

Benign:1

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.64

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.0040

T;.;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.83

T;T;T

MetaRNN

Benign

0.0015

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.4

N;.;N

REVEL

Benign

0.067

Sift

Uncertain

0.0050

D;.;D

Sift4G

Uncertain

0.023

D;D;D

Polyphen

0.84

P;.;.

Vest4

0.072

MPC

0.071

ClinPred

0.020

GERP RS

3.7

Varity_R

0.097

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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