chr4-143880509-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 17/23 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. G13A) has been classified as Benign.

• 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
• Publications: 16 publications found

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]

GUSBP5 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198682.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPE	NM_198682.3	MANE Select	c.38G>A	p.Gly13Glu	missense splice_region	Exon 2 of 4	NP_941391.2
	GYPE	NM_002102.4		c.38G>A	p.Gly13Glu	missense splice_region	Exon 2 of 4	NP_002093.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPE	ENST00000358615.9	TSL:1 MANE Select	c.38G>A	p.Gly13Glu	missense splice_region	Exon 2 of 4	ENSP00000351430.4
	GYPE	ENST00000437468.2	TSL:1	c.38G>A	p.Gly13Glu	missense splice_region	Exon 2 of 4	ENSP00000400698.2
	GYPE	ENST00000506264.5	TSL:5	n.38G>A		splice_region non_coding_transcript_exon	Exon 2 of 4	ENSP00000426746.1

Frequencies

GnomAD3 genomes AF: 0.509 AC: 76672 AN: 150612 Hom.: 12859 Cov.: 43

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

GnomAD2 exomes AF: 0.476 AC: 99425 AN: 208744 AF XY: 0.469

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 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

African (AFR) AF: 0.600 AC: 20032 AN: 33402

American (AMR) AF: 0.405 AC: 18000 AN: 44426

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 11444 AN: 25892

East Asian (EAS) AF: 0.583 AC: 23086 AN: 39596

South Asian (SAS) AF: 0.414 AC: 35511 AN: 85686

European-Finnish (FIN) AF: 0.420 AC: 22229 AN: 52960

Middle Eastern (MID) AF: 0.414 AC: 2368 AN: 5718

European-Non Finnish (NFE) AF: 0.459 AC: 506797 AN: 1104134

Other (OTH) AF: 0.466 AC: 27948 AN: 59952

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

African (AFR) AF: 0.609 AC: 25039 AN: 41100

American (AMR) AF: 0.459 AC: 6943 AN: 15118

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1557 AN: 3432

East Asian (EAS) AF: 0.595 AC: 3062 AN: 5144

South Asian (SAS) AF: 0.436 AC: 2062 AN: 4732

European-Finnish (FIN) AF: 0.422 AC: 4426 AN: 10486

Middle Eastern (MID) AF: 0.424 AC: 123 AN: 290

European-Non Finnish (NFE) AF: 0.474 AC: 31950 AN: 67426

Other (OTH) AF: 0.508 AC: 1065 AN: 2096

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 v4.9

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
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
MetaSVM	Benign	-0.98	T
PhyloP100		-2.4
PrimateAI	Benign	0.32	T
PROVEAN	Benign	3.5	N
REVEL	Benign	0.0080
Sift	Benign	0.94	T
Sift4G	Benign	1.0	T
Polyphen		0.0030	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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1132785; hg19: chr4-144801662; COSMIC: COSV62261325;