chr2-126678893-G-T

Position:

• chr2-126678893-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000259254.9(GYPC):​c.50-11362G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0738 in 152,228 control chromosomes in the GnomAD database, including 436 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 0.074 (433 hom., cov: 33)
  • Exomes 𝑓: 0.18 (3 hom.)
• Consequence: GYPC ENST00000259254.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GYPC	NM_002101.5	c.50-11362G>T		intron_variant		ENST00000259254.9	NP_002092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GYPC	ENST00000259254.9	c.50-11362G>T		intron_variant		1	NM_002101.5	ENSP00000259254	P2
GYPC	ENST00000356887.12	c.-832-6935G>T		intron_variant		1		ENSP00000349354	A2
GYPC	ENST00000409836.3	c.50-14971G>T		intron_variant		1		ENSP00000386904	A2
GYPC	ENST00000459787.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0738 AC: 11212 AN: 152018 Hom.: 434 Cov.: 33

Gnomad AFR AF: 0.0704

Gnomad AMI AF: 0.0670

Gnomad AMR AF: 0.0485

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0881

Gnomad FIN AF: 0.0623

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0857

Gnomad OTH AF: 0.0862

GnomAD4 exome AF: 0.185 AC: 17 AN: 92 Hom.: 3 Cov.: 0 AF XY: 0.152 AC XY: 10 AN XY: 66

Gnomad4 FIN exome AF: 0.194

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0737 AC: 11210 AN: 152136 Hom.: 433 Cov.: 33 AF XY: 0.0727 AC XY: 5410 AN XY: 74366

Gnomad4 AFR AF: 0.0703

Gnomad4 AMR AF: 0.0484

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0888

Gnomad4 FIN AF: 0.0623

Gnomad4 NFE AF: 0.0857

Gnomad4 OTH AF: 0.0848

Alfa AF: 0.0711 Hom.: 218

Bravo AF: 0.0712

Asia WGS AF: 0.0590 AC: 204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.13
DANN	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs13034269; hg19: chr2-127436469;