3-101254014-A-G

Position:

• chr3-101254014-A-G

Variant summary

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

The NM_016247.4(IMPG2):​c.1154-233T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,088 control chromosomes in the GnomAD database, including 1,316 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 0.13 (1316 hom., cov: 32)
• Consequence: IMPG2 NM_016247.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

Genes affected

IMPG2 (HGNC:18362): (interphotoreceptor matrix proteoglycan 2) The protein encoded by this gene binds chondroitin sulfate and hyaluronan and is a proteoglycan. The encoded protein plays a role in the organization of the interphotoreceptor matrix and may promote the growth and maintenance of the light-sensitive photoreceptor outer segment. Defects in this gene are a cause of retinitis pigmentosa type 56 and maculopathy, IMPG2-related.[provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMPG2	NM_016247.4	c.1154-233T>C		intron_variant		ENST00000193391.8	NP_057331.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMPG2	ENST00000193391.8	c.1154-233T>C		intron_variant		1	NM_016247.4	ENSP00000193391	P1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19498 AN: 151970 Hom.: 1315 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0945

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.128 AC: 19501 AN: 152088 Hom.: 1316 Cov.: 32 AF XY: 0.128 AC XY: 9512 AN XY: 74388

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.0945

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.143

Alfa AF: 0.134 Hom.: 619

Bravo AF: 0.128

Asia WGS AF: 0.181 AC: 626 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.6
DANN	Benign	0.92

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: rs3732893; hg19: chr3-100972858;