Variant 2-240456086-T-C 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.167-2944T>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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.770

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=-0.78).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
GPC1	NM_002081.3 linkuse as main transcript	c.167-2944T>C	intron_variant		ENST00000264039.7	NP_002072.2
MIR149	NR_029702.1 linkuse as main transcript	n.86T>C	non_coding_transcript_exon_variant	1/1
GPC1-AS1	NR_161169.1 linkuse as main transcript	n.104+511A>G	intron_variant, non_coding_transcript_variant
GPC1	XM_047443961.1 linkuse as main transcript	c.-202T>C	5_prime_UTR_variant	1/9		XP_047299917.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPC1	ENST00000264039.7 linkuse as main transcript	c.167-2944T>C	intron_variant		1	NM_002081.3	ENSP00000264039	P1	P35052-1
MIR149	ENST00000384879.1 linkuse as main transcript	n.86T>C	non_coding_transcript_exon_variant	1/1
GPC1-AS1	ENST00000404327.3 linkuse as main transcript	n.118+511A>G	intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.689

AC:

104698

AN:

151970

Hom.:

36499

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.628

AC XY:

62096

AN XY:

98922

show subpopulations

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.:

AF XY:

0.683

AC XY:

50764

AN XY:

74332

show subpopulations

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

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

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