2-126693955-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002101.5(GYPC):c.190+8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00292 in 1,582,978 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (60 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (59 hom.)
• Consequence: GYPC NM_002101.5 splice_region, intron
• Scores: Splicing: ADA: 0.00001007
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.877

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 2-126693955-C-G is Benign according to our data. Variant chr2-126693955-C-G is described in ClinVar as [Benign]. Clinvar id is 779867.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GYPC	NM_002101.5	c.190+8C>G		splice_region_variant, intron_variant		ENST00000259254.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GYPC	ENST00000259254.9	c.190+8C>G		splice_region_variant, intron_variant		1	NM_002101.5	P2
GYPC	ENST00000356887.12	c.127+8C>G		splice_region_variant, intron_variant		1		A2
GYPC	ENST00000409836.3	c.133+8C>G		splice_region_variant, intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2284 AN: 152086 Hom.: 61 Cov.: 32

Gnomad AFR AF: 0.0520

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00512

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.00403 AC: 1013 AN: 251234 Hom.: 25 AF XY: 0.00305 AC XY: 414 AN XY: 135780

Gnomad AFR exome AF: 0.0540

Gnomad AMR exome AF: 0.00205

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000784

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000220

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00163 AC: 2335 AN: 1430774 Hom.: 59 Cov.: 27 AF XY: 0.00147 AC XY: 1050 AN XY: 713670

Gnomad4 AFR exome AF: 0.0537

Gnomad4 AMR exome AF: 0.00266

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000630

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000115

Gnomad4 OTH exome AF: 0.00404

GnomAD4 genome AF: 0.0150 AC: 2290 AN: 152204 Hom.: 60 Cov.: 32 AF XY: 0.0154 AC XY: 1145 AN XY: 74418

Gnomad4 AFR AF: 0.0520

Gnomad4 AMR AF: 0.00511

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.00433 Hom.: 2

Bravo AF: 0.0172

Asia WGS AF: 0.00578 AC: 21 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

GYPC-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 14, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.18
Dann	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000010
dbscSNV1_RF	Benign	0.0
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: rs28387219; hg19: chr2-127451531;