chr2-240456083-A-G

Position:

• chr2-240456083-A-G

Variant summary

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

The ENST00000264039.7(GPC1):​c.167-2947A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 342,110 control chromosomes in the GnomAD database, including 2,708 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 (1413 hom., cov: 35)
  • Exomes 𝑓: 0.11 (1295 hom.)
• Consequence: GPC1 ENST00000264039.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.33

Genes affected

GPC1 (HGNC:4449): (glypican 1) Cell surface heparan sulfate proteoglycans are composed of a membrane-associated protein core substituted with a variable number of heparan sulfate chains. Members of the glypican-related integral membrane proteoglycan family (GRIPS) contain a core protein anchored to the cytoplasmic membrane via a glycosyl phosphatidylinositol linkage. These proteins may play a role in the control of cell division and growth regulation. [provided by RefSeq, Jul 2008]

MIR149 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPC1	NM_002081.3	c.167-2947A>G		intron_variant		ENST00000264039.7	NP_002072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPC1	ENST00000264039.7	c.167-2947A>G		intron_variant		1	NM_002081.3	ENSP00000264039.2

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20274 AN: 152104 Hom.: 1413 Cov.: 35

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.0885

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.143

GnomAD3 exomes AF: 0.112 AC: 3827 AN: 34320 Hom.: 258 AF XY: 0.111 AC XY: 2202 AN XY: 19878

Gnomad AFR exome AF: 0.0760

Gnomad AMR exome AF: 0.168

Gnomad ASJ exome AF: 0.0769

Gnomad EAS exome AF: 0.125

Gnomad SAS exome AF: 0.0847

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.102

Gnomad OTH exome AF: 0.0946

GnomAD4 exome AF: 0.105 AC: 20027 AN: 189900 Hom.: 1295 Cov.: 0 AF XY: 0.105 AC XY: 11373 AN XY: 108698

Gnomad4 AFR exome AF: 0.0857

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.0681

Gnomad4 EAS exome AF: 0.0953

Gnomad4 SAS exome AF: 0.0980

Gnomad4 FIN exome AF: 0.121

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.0970

GnomAD4 genome AF: 0.133 AC: 20276 AN: 152210 Hom.: 1413 Cov.: 35 AF XY: 0.135 AC XY: 10016 AN XY: 74416

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.0885

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.142

Alfa AF: 0.136 Hom.: 168

Bravo AF: 0.136

Asia WGS AF: 0.143 AC: 495 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.67
DANN	Benign	0.58

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: rs71428439; hg19: chr2-241395500; COSMIC: COSV50862663; COSMIC: COSV50862663;