rs17741574

Positions:

• chr2-126669121-C-T

Variant summary

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

The NM_002101.5(GYPC):​c.49+12809C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,118 control chromosomes in the GnomAD database, including 8,063 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 0.30 (8063 hom., cov: 33)
• Consequence: GYPC NM_002101.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.906

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GYPC	NM_002101.5	c.49+12809C>T		intron_variant		ENST00000259254.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GYPC	ENST00000259254.9	c.49+12809C>T		intron_variant		1	NM_002101.5	P2
GYPC	ENST00000356887.12	c.-833+12809C>T		intron_variant		1		A2
GYPC	ENST00000409836.3	c.49+12809C>T		intron_variant		1		A2
GYPC	ENST00000459787.1	n.172-9180C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45770 AN: 152000 Hom.: 8065 Cov.: 33

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.0741

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.312

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.301 AC: 45781 AN: 152118 Hom.: 8063 Cov.: 33 AF XY: 0.296 AC XY: 22047 AN XY: 74374

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.0739

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.310

Alfa AF: 0.369 Hom.: 12966

Bravo AF: 0.280

Asia WGS AF: 0.147 AC: 515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.36

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: rs17741574; hg19: chr2-127426697;