rs3734311

Variant names:

Variant summary

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

The NM_001563.4(IMPG1):c.1552C>G(p.His518Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 1,613,124 control chromosomes in the GnomAD database, including 147,619 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16804 hom., cov: 33)

Exomes 𝑓: 0.42 ( 130815 hom. )

Consequence

IMPG1
NM_001563.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.709

Publications

24 publications found

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 Gene-Disease associations (from GenCC):

inherited retinal dystrophy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
vitelliform macular dystrophy 4
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Laboratory for Molecular Medicine, ClinGen, G2P, Labcorp Genetics (formerly Invitae)
retinitis pigmentosa
Inheritance: AR, AD Classification: MODERATE Submitted by: Franklin by Genoox
adult-onset foveomacular vitelliform dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

IMPG1 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 (MetaRNN=2.6915104E-6).

BP6

Variant 6-75950834-G-C is Benign according to our data. Variant chr6-75950834-G-C is described in ClinVar as Benign. ClinVar VariationId is 1165049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001563.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPG1	NM_001563.4	MANE Select	c.1552C>G	p.His518Asp	missense	Exon 13 of 17	NP_001554.2
	IMPG1	NM_001282368.2		c.1318C>G	p.His440Asp	missense	Exon 12 of 16	NP_001269297.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPG1	ENST00000369950.8	TSL:1 MANE Select	c.1552C>G	p.His518Asp	missense	Exon 13 of 17	ENSP00000358966.3
	IMPG1	ENST00000611179.4	TSL:5	c.1318C>G	p.His440Asp	missense	Exon 12 of 16	ENSP00000481913.1

Frequencies

GnomAD3 genomes

AF:

0.463

AC:

70434

AN:

151974

Hom.:

16773

Cov.:

show subpopulations

Gnomad AFR

AF:

0.541

Gnomad AMI

AF:

0.567

Gnomad AMR

AF:

0.520

Gnomad ASJ

AF:

0.486

Gnomad EAS

AF:

0.671

Gnomad SAS

AF:

0.498

Gnomad FIN

AF:

0.416

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.390

Gnomad OTH

AF:

0.470

GnomAD2 exomes

AF:

0.468

AC:

117139

AN:

250304

AF XY:

0.461

show subpopulations

Gnomad AFR exome

AF:

0.535

Gnomad AMR exome

AF:

0.583

Gnomad ASJ exome

AF:

0.464

Gnomad EAS exome

AF:

0.677

Gnomad FIN exome

AF:

0.402

Gnomad NFE exome

AF:

0.396

Gnomad OTH exome

AF:

0.458

GnomAD4 exome

AF:

0.417

AC:

609141

AN:

1461030

Hom.:

130815

Cov.:

AF XY:

0.418

AC XY:

303811

AN XY:

726818

show subpopulations

African (AFR)

AF:

0.540

AC:

18070

AN:

33460

American (AMR)

AF:

0.575

AC:

25641

AN:

44598

Ashkenazi Jewish (ASJ)

AF:

0.464

AC:

12120

AN:

26128

East Asian (EAS)

AF:

0.674

AC:

26766

AN:

39686

South Asian (SAS)

AF:

0.492

AC:

42428

AN:

86238

European-Finnish (FIN)

AF:

0.398

AC:

21209

AN:

53326

Middle Eastern (MID)

AF:

0.459

AC:

2645

AN:

5762

European-Non Finnish (NFE)

AF:

0.390

AC:

433510

AN:

1111472

Other (OTH)

AF:

0.443

AC:

26752

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

19555

39110

58666

78221

97776

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13866

27732

41598

55464

69330

<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:

0.464

AC:

70518

AN:

152094

Hom.:

16804

Cov.:

AF XY:

0.468

AC XY:

34825

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.542

AC:

22469

AN:

41468

American (AMR)

AF:

0.520

AC:

7944

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.486

AC:

1686

AN:

3470

East Asian (EAS)

AF:

0.671

AC:

3479

AN:

5184

South Asian (SAS)

AF:

0.498

AC:

2405

AN:

4826

European-Finnish (FIN)

AF:

0.416

AC:

4403

AN:

10580

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.390

AC:

26506

AN:

67976

Other (OTH)

AF:

0.465

AC:

983

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1955

3910

5864

7819

9774

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:

0.415

Hom.:

10283

Bravo

AF:

0.477

TwinsUK

AF:

0.382

AC:

1418

ALSPAC

AF:

0.395

AC:

1522

ESP6500AA

AF:

0.520

AC:

2293

ESP6500EA

AF:

0.405

AC:

3486

ExAC

AF:

0.465

AC:

56449

Asia WGS

AF:

0.570

AC:

1982

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Benign concentric annular macular dystrophy (1)

Retinal dystrophy (1)

Vitelliform macular dystrophy 4 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.5

(source)

DANN

Benign

0.43

DEOGEN2

Benign

0.000033

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00025

LIST_S2

Benign

0.16

MetaRNN

Benign

0.0000027

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.3

PhyloP100

0.71

PrimateAI

Benign

0.29

PROVEAN

Benign

1.8

REVEL

Benign

0.061

Sift

Benign

1.0

Sift4G

Benign

0.72

Polyphen

0.0

Vest4

0.025

MPC

0.013

ClinPred

0.0013

GERP RS

1.5

Varity_R

0.058

gMVP

0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over