6-76037233-G-C

Variant names:

• chr6-76037233-G-C
• rs2765808
• NM_001563.4:c.302-2446C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001563.4(IMPG1):​c.302-2446C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 152,040 control chromosomes in the GnomAD database, including 29,182 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 0.62 (29182 hom., cov: 32)
• Consequence: IMPG1 NM_001563.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368
• Publications: 0 publications found

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):

• IMPG1-related dominant retinopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• vitelliform macular dystrophy 4

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P
• IMPG1-related recessive retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa

  Inheritance: AR, AD Classification: MODERATE Submitted by: Franklin by Genoox
• adult-onset foveomacular vitelliform dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.637 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPG1	NM_001563.4	MANE Select	c.302-2446C>G		intron	N/A	NP_001554.2
	IMPG1	NM_001282368.2		c.68-2446C>G		intron	N/A	NP_001269297.1	A0A087WYL3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPG1	ENST00000369950.8	TSL:1 MANE Select	c.302-2446C>G		intron	N/A	ENSP00000358966.3	Q17R60-1
	IMPG1	ENST00000611179.4	TSL:5	c.68-2446C>G		intron	N/A	ENSP00000481913.1	A0A087WYL3
	IMPG1	ENST00000369963.5	TSL:5	c.47-2446C>G		intron	N/A	ENSP00000358980.4	A0A0R4J2E9

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93710 AN: 151922 Hom.: 29153 Cov.: 32

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.590

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.617 AC: 93796 AN: 152040 Hom.: 29182 Cov.: 32 AF XY: 0.616 AC XY: 45793 AN XY: 74318

African (AFR) AF: 0.605 AC: 25087 AN: 41440

American (AMR) AF: 0.571 AC: 8723 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2121 AN: 3468

East Asian (EAS) AF: 0.475 AC: 2447 AN: 5150

South Asian (SAS) AF: 0.640 AC: 3090 AN: 4826

European-Finnish (FIN) AF: 0.628 AC: 6638 AN: 10572

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.642 AC: 43634 AN: 67980

Other (OTH) AF: 0.593 AC: 1251 AN: 2108

Alfa AF: 0.628 Hom.: 3777

Bravo AF: 0.611

Asia WGS AF: 0.560 AC: 1950 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	16
DANN	Benign	0.41
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.43		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.43		Position offset: 1

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

Other links and lift over

dbSNP: rs2765808; hg19: chr6-76746950; COSMIC: COSV64061176;