rs935019

Variant names:

• chr2-126688913-A-G
• rs935019
• NM_002101.5:c.50-1342A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-126688913-A-G
• chr2-126688913-A-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.50-1342A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 151,728 control chromosomes in the GnomAD database, including 4,058 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 0.22 (4058 hom., cov: 32)
• Consequence: GYPC NM_002101.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• 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 = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYPC	NM_002101.5	c.50-1342A>G		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.50-1342A>G		intron_variant	Intron 1 of 3	1	NM_002101.5	ENSP00000259254.4
GYPC	ENST00000409836.3	c.50-4951A>G		intron_variant	Intron 1 of 2	1		ENSP00000386904.3
GYPC	ENST00000356887.12	c.-14-1342A>G		intron_variant	Intron 2 of 4	1		ENSP00000349354.7

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33321 AN: 151606 Hom.: 4057 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.220 AC: 33343 AN: 151728 Hom.: 4058 Cov.: 32 AF XY: 0.219 AC XY: 16228 AN XY: 74192

African (AFR) AF: 0.130 AC: 5325 AN: 41074

American (AMR) AF: 0.173 AC: 2645 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1028 AN: 3472

East Asian (EAS) AF: 0.236 AC: 1222 AN: 5184

South Asian (SAS) AF: 0.258 AC: 1243 AN: 4816

European-Finnish (FIN) AF: 0.266 AC: 2813 AN: 10588

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.270 AC: 18366 AN: 67988

Other (OTH) AF: 0.240 AC: 506 AN: 2112

Alfa AF: 0.196 Hom.: 763

Bravo AF: 0.208

Asia WGS AF: 0.252 AC: 878 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	0.48
DANN	Benign	0.45
PhyloP100		-0.033
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: rs935019; hg19: chr2-127446489;