rs7589096

chr2-126665017-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+8705C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0907 in 152,172 control chromosomes in the GnomAD database, including 694 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 0.091 (694 hom., cov: 33)
• Consequence: GYPC NM_002101.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GYPC	NM_002101.5	c.49+8705C>T		intron_variant		ENST00000259254.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GYPC	ENST00000259254.9	c.49+8705C>T		intron_variant		1	NM_002101.5	P2
GYPC	ENST00000356887.12	c.-833+8705C>T		intron_variant		1		A2
GYPC	ENST00000409836.3	c.49+8705C>T		intron_variant		1		A2
GYPC	ENST00000459787.1	n.171+8705C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0908 AC: 13803 AN: 152054 Hom.: 694 Cov.: 33

Gnomad AFR AF: 0.0989

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.0704

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0123

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0633

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.0930

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.0907 AC: 13803 AN: 152172 Hom.: 694 Cov.: 33 AF XY: 0.0899 AC XY: 6686 AN XY: 74404

Gnomad4 AFR AF: 0.0988

Gnomad4 AMR AF: 0.0702

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.0123

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.0633

Gnomad4 NFE AF: 0.0930

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0950 Hom.: 525

Bravo AF: 0.0907

Asia WGS AF: 0.0890 AC: 308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.5
Dann	Benign	0.57

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: rs7589096; hg19: chr2-127422593;