2-126695903-G-A

Position:

• chr2-126695903-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002101.5(GYPC):​c.191-43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,541,388 control chromosomes in the GnomAD database, including 44,526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6632 hom., cov: 33)
  • Exomes 𝑓: 0.23 (37894 hom.)
• Consequence: GYPC NM_002101.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.619

Genes affected

GYPC (HGNC:4704): (glycophorin C (Gerbich blood group)) Glycophorin C (GYPC) is an integral membrane glycoprotein. It is a minor species carried by human erythrocytes, but plays an important role in regulating the mechanical stability of red cells. A number of glycophorin C mutations have been described. The Gerbich and Yus phenotypes are due to deletion of exon 3 and 2, respectively. The Webb and Duch antigens, also known as glycophorin D, result from single point mutations of the glycophorin C gene. The glycophorin C protein has very little homology with glycophorins A and B. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-126695903-G-A is Benign according to our data. Variant chr2-126695903-G-A is described in ClinVar as [Benign]. Clinvar id is 1258136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GYPC	NM_002101.5	c.191-43G>A		intron_variant		ENST00000259254.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GYPC	ENST00000259254.9	c.191-43G>A		intron_variant		1	NM_002101.5	P2
GYPC	ENST00000356887.12	c.128-43G>A		intron_variant		1		A2
GYPC	ENST00000409836.3	c.134-43G>A		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42382 AN: 151932 Hom.: 6618 Cov.: 33

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.281

GnomAD3 exomes AF: 0.248 AC: 61770 AN: 249060 Hom.: 8504 AF XY: 0.237 AC XY: 31985 AN XY: 134784

Gnomad AFR exome AF: 0.411

Gnomad AMR exome AF: 0.317

Gnomad ASJ exome AF: 0.186

Gnomad EAS exome AF: 0.423

Gnomad SAS exome AF: 0.145

Gnomad FIN exome AF: 0.191

Gnomad NFE exome AF: 0.220

Gnomad OTH exome AF: 0.227

GnomAD4 exome AF: 0.227 AC: 315186 AN: 1389338 Hom.: 37894 Cov.: 23 AF XY: 0.222 AC XY: 154601 AN XY: 695612

Gnomad4 AFR exome AF: 0.420

Gnomad4 AMR exome AF: 0.318

Gnomad4 ASJ exome AF: 0.189

Gnomad4 EAS exome AF: 0.348

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.195

Gnomad4 NFE exome AF: 0.221

Gnomad4 OTH exome AF: 0.235

GnomAD4 genome AF: 0.279 AC: 42441 AN: 152050 Hom.: 6632 Cov.: 33 AF XY: 0.279 AC XY: 20769 AN XY: 74328

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.278

Alfa AF: 0.242 Hom.: 1020

Bravo AF: 0.300

Asia WGS AF: 0.253 AC: 878 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.88
DANN	Benign	0.55

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

Other links and lift over

dbSNP: rs4538146; hg19: chr2-127453479; COSMIC: COSV52146562;