rs71428439

Variant names:

• chr2-240456083-A-G
• rs71428439
• NM_002081.3:c.167-2947A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 42 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GPC1	NM_002081.3	c.167-2947A>G		intron_variant	Intron 1 of 8	ENST00000264039.7	NP_002072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC1	ENST00000264039.7	c.167-2947A>G		intron_variant	Intron 1 of 8	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

GnomAD2 exomes AF: 0.112 AC: 3827 AN: 34320 AF XY: 0.111

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 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

African (AFR) AF: 0.0857 AC: 184 AN: 2146

American (AMR) AF: 0.138 AC: 1254 AN: 9110

Ashkenazi Jewish (ASJ) AF: 0.0681 AC: 376 AN: 5520

East Asian (EAS) AF: 0.0953 AC: 155 AN: 1626

South Asian (SAS) AF: 0.0980 AC: 4163 AN: 42468

European-Finnish (FIN) AF: 0.121 AC: 2090 AN: 17290

Middle Eastern (MID) AF: 0.0735 AC: 136 AN: 1850

European-Non Finnish (NFE) AF: 0.107 AC: 10831 AN: 101248

Other (OTH) AF: 0.0970 AC: 838 AN: 8642

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

African (AFR) AF: 0.116 AC: 4832 AN: 41538

American (AMR) AF: 0.179 AC: 2737 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0885 AC: 307 AN: 3468

East Asian (EAS) AF: 0.192 AC: 990 AN: 5146

South Asian (SAS) AF: 0.112 AC: 542 AN: 4828

European-Finnish (FIN) AF: 0.133 AC: 1417 AN: 10618

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.132 AC: 8958 AN: 68004

Other (OTH) AF: 0.142 AC: 300 AN: 2112

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
PhyloP100		-6.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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