rs17741574

Variant names:

• chr2-126669121-C-T
• rs17741574
• NM_002101.5:c.49+12809C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

GYPC Gene-Disease associations (from GenCC):

• hereditary elliptocytosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GYPC	NM_002101.5	c.49+12809C>T		intron_variant	Intron 1 of 3	ENST00000259254.9	NP_002092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GYPC	ENST00000259254.9	c.49+12809C>T		intron_variant	Intron 1 of 3	1	NM_002101.5	ENSP00000259254.4
GYPC	ENST00000409836.3	c.49+12809C>T		intron_variant	Intron 1 of 2	1		ENSP00000386904.3
GYPC	ENST00000356887.12	c.-833+12809C>T		intron_variant	Intron 1 of 4	1		ENSP00000349354.7
GYPC	ENST00000459787.1	n.172-9180C>T		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.151 AC: 6252 AN: 41516

American (AMR) AF: 0.268 AC: 4097 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1151 AN: 3470

East Asian (EAS) AF: 0.0739 AC: 383 AN: 5182

South Asian (SAS) AF: 0.201 AC: 972 AN: 4824

European-Finnish (FIN) AF: 0.398 AC: 4200 AN: 10564

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27550 AN: 67964

Other (OTH) AF: 0.310 AC: 654 AN: 2112

Alfa AF: 0.341 Hom.: 18361

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
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism (auto)

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: rs17741574; hg19: chr2-127426697;