2-240462246-C-T

Variant names:

• chr2-240462246-C-T
• rs61737161
• NM_002081.3:c.381C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_002081.3(GPC1):​c.381C>T​(p.Pro127Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,610,318 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0094 (20 hom., cov: 33)
  • Exomes 𝑓: 0.00095 (21 hom.)
• Consequence: GPC1 NM_002081.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.77
• Publications: 0 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]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.033).
• BP6: Variant 2-240462246-C-T is Benign according to our data. Variant chr2-240462246-C-T is described in ClinVar as Benign. ClinVar VariationId is 790521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.77 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00938 (1429/152314) while in subpopulation AFR AF = 0.0328 (1361/41554). AF 95% confidence interval is 0.0313. There are 20 homozygotes in GnomAd4. There are 659 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 20 gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC1	NM_002081.3	MANE Select	c.381C>T	p.Pro127Pro	synonymous	Exon 3 of 9	NP_002072.2	A0A384NPH9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC1	ENST00000264039.7	TSL:1 MANE Select	c.381C>T	p.Pro127Pro	synonymous	Exon 3 of 9	ENSP00000264039.2	P35052-1
	GPC1	ENST00000495100.1	TSL:1	n.1058C>T		non_coding_transcript_exon	Exon 2 of 7
	GPC1	ENST00000943307.1		c.537C>T	p.Pro179Pro	synonymous	Exon 4 of 10	ENSP00000613366.1

Frequencies

GnomAD3 genomes AF: 0.00937 AC: 1426 AN: 152196 Hom.: 20 Cov.: 33

Gnomad AFR AF: 0.0328

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00716

GnomAD2 exomes AF: 0.00228 AC: 553 AN: 242908 AF XY: 0.00163

Gnomad AFR exome AF: 0.0341

Gnomad AMR exome AF: 0.000673

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000458

Gnomad OTH exome AF: 0.000674

GnomAD4 exome AF: 0.000950 AC: 1385 AN: 1458004 Hom.: 21 Cov.: 33 AF XY: 0.000795 AC XY: 576 AN XY: 724972

African (AFR) AF: 0.0355 AC: 1185 AN: 33424

American (AMR) AF: 0.00128 AC: 57 AN: 44556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26042

East Asian (EAS) AF: 0.00 AC: 0 AN: 39596

South Asian (SAS) AF: 0.0000582 AC: 5 AN: 85914

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51996

Middle Eastern (MID) AF: 0.000709 AC: 4 AN: 5642

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1110652

Other (OTH) AF: 0.00193 AC: 116 AN: 60182

GnomAD4 genome AF: 0.00938 AC: 1429 AN: 152314 Hom.: 20 Cov.: 33 AF XY: 0.00885 AC XY: 659 AN XY: 74488

African (AFR) AF: 0.0328 AC: 1361 AN: 41554

American (AMR) AF: 0.00320 AC: 49 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68030

Other (OTH) AF: 0.00709 AC: 15 AN: 2116

Alfa AF: 0.00623 Hom.: 4

Bravo AF: 0.0109

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.3
DANN	Benign	0.82
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism

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: rs61737161; hg19: chr2-241401663; COSMIC: COSV99883377; COSMIC: COSV99883377;