rs71428439

Positions:

• chr2-240456083-A-G

Variant summary

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

The NM_002081.3(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 NM_002081.3 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:31536): (microRNA 149) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

GPC1-AS1 (HGNC:56102): (GPC1 antisense RNA 1)

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	UniProt
GPC1	NM_002081.3	c.167-2947A>G		intron_variant		ENST00000264039.7
MIR149	NR_029702.1	n.83A>G		non_coding_transcript_exon_variant	1/1
GPC1-AS1	NR_161169.1	n.104+514T>C		intron_variant, non_coding_transcript_variant
GPC1	XM_047443961.1	c.-205A>G		5_prime_UTR_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPC1	ENST00000264039.7	c.167-2947A>G		intron_variant		1	NM_002081.3	P1
MIR149	ENST00000384879.1	n.83A>G		non_coding_transcript_exon_variant	1/1
GPC1-AS1	ENST00000404327.3	n.118+514T>C		intron_variant, non_coding_transcript_variant		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;