6-76007025-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IMPG1	NM_001563.4	c.887+455G>A		intron_variant		ENST00000369950.8
IMPG1	NM_001282368.2	c.653+455G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IMPG1	ENST00000369950.8	c.887+455G>A		intron_variant		1	NM_001563.4	P2
IMPG1	ENST00000611179.4	c.653+455G>A		intron_variant		5		A2

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

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.367

Alfa AF: 0.344 Hom.: 2634

Bravo AF: 0.362

Asia WGS AF: 0.393 AC: 1366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	13
Dann	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs1886985; hg19: chr6-76716742;