6-76007025-C-T

Variant names:

• chr6-76007025-C-T
• rs1886985
• NM_001563.4:c.887+455G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001563.4(IMPG1):​c.887+455G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 151,802 control chromosomes in the GnomAD database, including 9,811 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 0.36 (9811 hom., cov: 31)
• Consequence: IMPG1 NM_001563.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.844
• Publications: 5 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):

• 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.474 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.887+455G>A		intron	N/A	NP_001554.2
	IMPG1	NM_001282368.2		c.653+455G>A		intron	N/A	NP_001269297.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPG1	ENST00000369950.8	TSL:1 MANE Select	c.887+455G>A		intron	N/A	ENSP00000358966.3
	IMPG1	ENST00000611179.4	TSL:5	c.653+455G>A		intron	N/A	ENSP00000481913.1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53878 AN: 151684 Hom.: 9811 Cov.: 31

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.355 AC: 53904 AN: 151802 Hom.: 9811 Cov.: 31 AF XY: 0.356 AC XY: 26412 AN XY: 74150

African (AFR) AF: 0.366 AC: 15152 AN: 41416

American (AMR) AF: 0.428 AC: 6536 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1163 AN: 3460

East Asian (EAS) AF: 0.490 AC: 2525 AN: 5158

South Asian (SAS) AF: 0.324 AC: 1553 AN: 4794

European-Finnish (FIN) AF: 0.343 AC: 3608 AN: 10522

Middle Eastern (MID) AF: 0.348 AC: 101 AN: 290

European-Non Finnish (NFE) AF: 0.328 AC: 22235 AN: 67880

Other (OTH) AF: 0.367 AC: 775 AN: 2112

Alfa AF: 0.349 Hom.: 3050

Bravo AF: 0.362

Asia WGS AF: 0.393 AC: 1366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	13
DANN	Benign	0.72
PhyloP100		0.84
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1886985; hg19: chr6-76716742;