chr2-126665490-G-T

Variant names:

• chr2-126665490-G-T
• rs4663038
• NM_002101.5:c.49+9178G>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+9178G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,138 control chromosomes in the GnomAD database, including 7,342 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 (7342 hom., cov: 33)
• Consequence: GYPC NM_002101.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 3 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 (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYPC	NM_002101.5	c.49+9178G>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+9178G>T		intron_variant	Intron 1 of 3	1	NM_002101.5	ENSP00000259254.4
GYPC	ENST00000409836.3	c.49+9178G>T		intron_variant	Intron 1 of 2	1		ENSP00000386904.3
GYPC	ENST00000356887.12	c.-833+9178G>T		intron_variant	Intron 1 of 4	1		ENSP00000349354.7
GYPC	ENST00000459787.1	n.171+9178G>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45242 AN: 152018 Hom.: 7327 Cov.: 33

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.298 AC: 45275 AN: 152138 Hom.: 7342 Cov.: 33 AF XY: 0.306 AC XY: 22719 AN XY: 74352

African (AFR) AF: 0.213 AC: 8831 AN: 41486

American (AMR) AF: 0.428 AC: 6542 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 921 AN: 3472

East Asian (EAS) AF: 0.548 AC: 2830 AN: 5164

South Asian (SAS) AF: 0.379 AC: 1831 AN: 4828

European-Finnish (FIN) AF: 0.358 AC: 3781 AN: 10576

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19689 AN: 67994

Other (OTH) AF: 0.288 AC: 609 AN: 2114

Alfa AF: 0.296 Hom.: 26471

Bravo AF: 0.304

Asia WGS AF: 0.431 AC: 1501 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	2.0
DANN	Benign	0.73
PhyloP100		0.36
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: rs4663038; hg19: chr2-127423066;