4-143880509-C-T

Variant names:

• chr4-143880509-C-T
• rs1132785
• NM_198682.3:c.38G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198682.3(GYPE):​c.38G>A​(p.Gly13Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 1,451,766 control chromosomes in the GnomAD database, including 102,929 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.51 (12874 hom., cov: 43)
  • Exomes 𝑓: 0.46 (102929 hom.)
  • Failed GnomAD Quality Control
• Consequence: GYPE NM_198682.3 missense, splice_region
• Scores: Splicing: ADA: 0.00007242
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.39

Genes affected

GYPE (HGNC:4705): (glycophorin E (MNS blood group)) The protein encoded by this gene is a sialoglycoprotein and a type I membrane protein. It is a member of a gene family with GPA and GPB genes. This encoded protein might carry the M blood group antigen. GYPA, GYPB, and GYPE are organized in tandem on chromosome 4. This gene might have derived from an ancestral gene common to the GPB gene by gene duplication. Two alternatively spliced transcript variants encoding the same protein have been described for this gene. [provided by RefSeq, Jul 2008]

ENSG00000251600 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.2594461E-4).
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYPE	NM_198682.3	c.38G>A	p.Gly13Glu	missense_variant, splice_region_variant	Exon 2 of 4	ENST00000358615.9	NP_941391.2
GYPE	NM_002102.4	c.38G>A	p.Gly13Glu	missense_variant, splice_region_variant	Exon 2 of 4		NP_002093.2
LOC105377459	XR_001741861.1	n.1463+14433C>T		intron_variant	Intron 9 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GYPE	ENST00000358615.9	c.38G>A	p.Gly13Glu	missense_variant, splice_region_variant	Exon 2 of 4	1	NM_198682.3	ENSP00000351430.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 76672 AN: 150612 Hom.: 12859 Cov.: 43 FAILED QC

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.504

GnomAD3 exomes AF: 0.476 AC: 99425 AN: 208744 Hom.: 16158 AF XY: 0.469 AC XY: 53129 AN XY: 113244

Gnomad AFR exome AF: 0.631

Gnomad AMR exome AF: 0.437

Gnomad ASJ exome AF: 0.487

Gnomad EAS exome AF: 0.629

Gnomad SAS exome AF: 0.437

Gnomad FIN exome AF: 0.416

Gnomad NFE exome AF: 0.467

Gnomad OTH exome AF: 0.478

GnomAD4 exome AF: 0.460 AC: 667415 AN: 1451766 Hom.: 102929 Cov.: 83 AF XY: 0.457 AC XY: 330017 AN XY: 722424

Gnomad4 AFR exome AF: 0.600

Gnomad4 AMR exome AF: 0.405

Gnomad4 ASJ exome AF: 0.442

Gnomad4 EAS exome AF: 0.583

Gnomad4 SAS exome AF: 0.414

Gnomad4 FIN exome AF: 0.420

Gnomad4 NFE exome AF: 0.459

Gnomad4 OTH exome AF: 0.466

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.509 AC: 76740 AN: 150732 Hom.: 12874 Cov.: 43 AF XY: 0.503 AC XY: 37041 AN XY: 73658

Gnomad4 AFR AF: 0.609

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.595

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.508

Alfa AF: 0.506 Hom.: 1405

Bravo AF: 0.771

ExAC AF: 0.431 AC: 52331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.0010
DANN	Benign	0.23
DEOGEN2	Benign	0.0041	T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.44	.;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.00013	T;T
MetaSVM	Benign	-0.98	T
PrimateAI	Benign	0.32	T
PROVEAN	Benign	3.5	N;N
REVEL	Benign	0.0080
Sift	Benign	0.94	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0030	B;B
Vest4		0.11
MPC		0.0068
ClinPred		0.00077	T
GERP RS		-3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.030
gMVP		0.027

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000072
dbscSNV1_RF	Benign	0.15
SpliceAI score (max)		0.030		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: rs1132785; hg19: chr4-144801662; COSMIC: COSV62261325;