2-240456086-T-C

Variant names:

• chr2-240456086-T-C
• rs2292832
• NM_002081.3:c.167-2944T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002081.3(GPC1):​c.167-2944T>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
• Publications: 277 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002081.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC1	NM_002081.3	MANE Select	c.167-2944T>C		intron	N/A	NP_002072.2
	MIR149	NR_029702.1		n.86T>C		non_coding_transcript_exon	Exon 1 of 1
	GPC1-AS1	NR_161169.1		n.104+511A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC1	ENST00000264039.7	TSL:1 MANE Select	c.167-2944T>C		intron	N/A	ENSP00000264039.2
	MIR149	ENST00000384879.1	TSL:6	n.86T>C		non_coding_transcript_exon	Exon 1 of 1
	GPC1	ENST00000420138.5	TSL:5	c.-50-2944T>C		intron	N/A	ENSP00000415077.2

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

GnomAD2 exomes AF: 0.589 AC: 19373 AN: 32884 AF XY: 0.595

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 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

African (AFR) AF: 0.673 AC: 1203 AN: 1788

American (AMR) AF: 0.531 AC: 4055 AN: 7634

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 3429 AN: 4750

East Asian (EAS) AF: 0.228 AC: 313 AN: 1372

South Asian (SAS) AF: 0.539 AC: 21517 AN: 39894

European-Finnish (FIN) AF: 0.663 AC: 10457 AN: 15782

Middle Eastern (MID) AF: 0.668 AC: 1136 AN: 1700

European-Non Finnish (NFE) AF: 0.691 AC: 63878 AN: 92448

Other (OTH) AF: 0.664 AC: 5225 AN: 7870

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

African (AFR) AF: 0.711 AC: 29506 AN: 41504

American (AMR) AF: 0.668 AC: 10224 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.759 AC: 2636 AN: 3472

East Asian (EAS) AF: 0.350 AC: 1792 AN: 5120

South Asian (SAS) AF: 0.557 AC: 2686 AN: 4822

European-Finnish (FIN) AF: 0.675 AC: 7137 AN: 10572

Middle Eastern (MID) AF: 0.729 AC: 213 AN: 292

European-Non Finnish (NFE) AF: 0.711 AC: 48350 AN: 67970

Other (OTH) AF: 0.704 AC: 1487 AN: 2112

Alfa AF: 0.703 Hom.: 46176

Bravo AF: 0.686

Asia WGS AF: 0.462 AC: 1602 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.74
PhyloP100		-0.77
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: rs2292832; hg19: chr2-241395503; COSMIC: COSV50866963; COSMIC: COSV50866963;