2-240456086-T-C

Position:

• chr2-240456086-T-C

Variant summary

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

The NM_002081.3(GPC1):​c.167-2944T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 325,312 control chromosomes in the GnomAD database, including 73,222 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 0.69 (36514 hom., cov: 35)
  • Exomes 𝑓: 0.64 (36708 hom.)
• Consequence: GPC1 NM_002081.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.770

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPC1	NM_002081.3	c.167-2944T>C		intron_variant		ENST00000264039.7	NP_002072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPC1	ENST00000264039.7	c.167-2944T>C		intron_variant		1	NM_002081.3	ENSP00000264039.2

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104698 AN: 151970 Hom.: 36499 Cov.: 35

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.759

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.711

GnomAD3 exomes AF: 0.589 AC: 19373 AN: 32884 Hom.: 5949 AF XY: 0.595 AC XY: 11299 AN XY: 18974

Gnomad AFR exome AF: 0.675

Gnomad AMR exome AF: 0.529

Gnomad ASJ exome AF: 0.710

Gnomad EAS exome AF: 0.254

Gnomad SAS exome AF: 0.485

Gnomad FIN exome AF: 0.648

Gnomad NFE exome AF: 0.659

Gnomad OTH exome AF: 0.634

GnomAD4 exome AF: 0.642 AC: 111213 AN: 173238 Hom.: 36708 Cov.: 0 AF XY: 0.628 AC XY: 62096 AN XY: 98922

Gnomad4 AFR exome AF: 0.673

Gnomad4 AMR exome AF: 0.531

Gnomad4 ASJ exome AF: 0.722

Gnomad4 EAS exome AF: 0.228

Gnomad4 SAS exome AF: 0.539

Gnomad4 FIN exome AF: 0.663

Gnomad4 NFE exome AF: 0.691

Gnomad4 OTH exome AF: 0.664

GnomAD4 genome AF: 0.689 AC: 104747 AN: 152074 Hom.: 36514 Cov.: 35 AF XY: 0.683 AC XY: 50764 AN XY: 74332

Gnomad4 AFR AF: 0.711

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.759

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.675

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.704

Alfa AF: 0.702 Hom.: 38436

Bravo AF: 0.686

Asia WGS AF: 0.462 AC: 1602 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.74

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: rs2292832; hg19: chr2-241395503; COSMIC: COSV50866963; COSMIC: COSV50866963;