Variant chr2-240456083-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -6.33

Variant links:

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]

GPC1 links:

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]

MIR149 links:

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

GPC1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Effect	#exon/exons	MANE
GPC1	NM_002081.3 linkuse as main transcript	c.167-2947A>G	intron_variant		ENST00000264039.7
MIR149	NR_029702.1 linkuse as main transcript	n.83A>G	non_coding_transcript_exon_variant	1/1
GPC1-AS1	NR_161169.1 linkuse as main transcript	n.104+514T>C	intron_variant, non_coding_transcript_variant
GPC1	XM_047443961.1 linkuse as main transcript	c.-205A>G	5_prime_UTR_variant	1/9

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPC1	ENST00000264039.7 linkuse as main transcript	c.167-2947A>G	intron_variant		1	NM_002081.3	P1	P35052-1
MIR149	ENST00000384879.1 linkuse as main transcript	n.83A>G	non_coding_transcript_exon_variant	1/1
GPC1-AS1	ENST00000404327.3 linkuse as main transcript	n.118+514T>C	intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20274

AN:

152104

Hom.:

1413

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.105

AC XY:

11373

AN XY:

108698

show subpopulations

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.:

AF XY:

0.135

AC XY:

10016

AN XY:

74416

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over