6-76037233-G-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMPG1	NM_001563.4	c.302-2446C>G		intron_variant	Intron 2 of 16	ENST00000369950.8	NP_001554.2
IMPG1	NM_001282368.2	c.68-2446C>G		intron_variant	Intron 1 of 15		NP_001269297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMPG1	ENST00000369950.8	c.302-2446C>G		intron_variant	Intron 2 of 16	1	NM_001563.4	ENSP00000358966.3
IMPG1	ENST00000611179.4	c.68-2446C>G		intron_variant	Intron 1 of 15	5		ENSP00000481913.1
IMPG1	ENST00000369963.5	c.47-2446C>G		intron_variant	Intron 2 of 5	5		ENSP00000358980.4

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

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.571

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.640

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.593

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	16
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

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