6-76025348-A-G

Variant names:

• chr6-76025348-A-G
• rs1341568
• NM_001563.4:c.498-90T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 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.498-90T>C		intron	N/A	NP_001554.2
	IMPG1	NM_001282368.2		c.264-90T>C		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.498-90T>C		intron	N/A	ENSP00000358966.3
	IMPG1	ENST00000611179.4	TSL:5	c.264-90T>C		intron	N/A	ENSP00000481913.1
	IMPG1	ENST00000369963.5	TSL:5	c.243-90T>C		intron	N/A	ENSP00000358980.4

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

African (AFR) AF: 0.344 AC: 4294 AN: 12476

American (AMR) AF: 0.393 AC: 8486 AN: 21614

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 4734 AN: 14648

East Asian (EAS) AF: 0.484 AC: 15122 AN: 31238

South Asian (SAS) AF: 0.338 AC: 13450 AN: 39796

European-Finnish (FIN) AF: 0.339 AC: 12810 AN: 37826

Middle Eastern (MID) AF: 0.365 AC: 871 AN: 2388

European-Non Finnish (NFE) AF: 0.331 AC: 98043 AN: 296060

Other (OTH) AF: 0.358 AC: 9274 AN: 25914

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

African (AFR) AF: 0.331 AC: 13750 AN: 41482

American (AMR) AF: 0.394 AC: 6020 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1162 AN: 3468

East Asian (EAS) AF: 0.493 AC: 2550 AN: 5170

South Asian (SAS) AF: 0.332 AC: 1602 AN: 4822

European-Finnish (FIN) AF: 0.343 AC: 3620 AN: 10566

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22291 AN: 67962

Other (OTH) AF: 0.365 AC: 771 AN: 2110

Alfa AF: 0.336 Hom.: 1725

Bravo AF: 0.347

Asia WGS AF: 0.394 AC: 1369 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.8
DANN	Benign	0.77
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1341568; hg19: chr6-76735065; COSMIC: COSV107476727;