6-76025348-A-G

Position:

• chr6-76025348-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001563.4(IMPG1):​c.498-90T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 634,036 control chromosomes in the GnomAD database, including 38,703 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 0.34 (9140 hom., cov: 32)
  • Exomes 𝑓: 0.35 (29563 hom.)
• Consequence: IMPG1 NM_001563.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IMPG1	NM_001563.4	c.498-90T>C		intron_variant		ENST00000369950.8
IMPG1	NM_001282368.2	c.264-90T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IMPG1	ENST00000369950.8	c.498-90T>C		intron_variant		1	NM_001563.4	P2
IMPG1	ENST00000369963.5	c.243-90T>C		intron_variant		5
IMPG1	ENST00000611179.4	c.264-90T>C		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52122 AN: 151958 Hom.: 9145 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.369

GnomAD4 exome AF: 0.347 AC: 167084 AN: 481960 Hom.: 29563 AF XY: 0.346 AC XY: 89546 AN XY: 258796

Gnomad4 AFR exome AF: 0.344

Gnomad4 AMR exome AF: 0.393

Gnomad4 ASJ exome AF: 0.323

Gnomad4 EAS exome AF: 0.484

Gnomad4 SAS exome AF: 0.338

Gnomad4 FIN exome AF: 0.339

Gnomad4 NFE exome AF: 0.331

Gnomad4 OTH exome AF: 0.358

GnomAD4 genome AF: 0.343 AC: 52127 AN: 152076 Hom.: 9140 Cov.: 32 AF XY: 0.344 AC XY: 25558 AN XY: 74328

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.365

Alfa AF: 0.336 Hom.: 1684

Bravo AF: 0.347

Asia WGS AF: 0.394 AC: 1369 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.8
DANN	Benign	0.77

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

LitVar

Other links and lift over

dbSNP: rs1341568; hg19: chr6-76735065;