rs1132785

Positions:

• chr4-143880509-C-G
• chr4-143880509-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_198682.3(GYPE):​c.38G>C​(p.Gly13Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. 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. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G13E) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.30 (4 hom., cov: 43)
  • Exomes 𝑓: 0.31 (5 hom.)
  • Failed GnomAD Quality Control
• Consequence: GYPE NM_198682.3 missense, splice_region
• Scores: Splicing: ADA: 0.001664
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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]

GUSBP5 (HGNC:42319): (GUSB pseudogene 5)

LOC105377459 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004680425).
• BP6: Variant 4-143880509-C-G is Benign according to our data. Variant chr4-143880509-C-G is described in ClinVar as [Benign]. Clinvar id is 402918.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GYPE	NM_198682.3	c.38G>C	p.Gly13Ala	missense_variant, splice_region_variant	2/4	ENST00000358615.9
LOC105377459	XR_001741861.1	n.1463+14433C>G		intron_variant, non_coding_transcript_variant
GYPE	NM_002102.4	c.38G>C	p.Gly13Ala	missense_variant, splice_region_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GYPE	ENST00000358615.9	c.38G>C	p.Gly13Ala	missense_variant, splice_region_variant	2/4	1	NM_198682.3	P1
GUSBP5	ENST00000641328.1	n.1315+14433C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00 AC: 39796 AN: 132948 Hom.: 4 Cov.: 43 FAILED QC

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.319

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.284

GnomAD3 exomes AF: 0.262 AC: 54614 AN: 208744 Hom.: 1 AF XY: 0.263 AC XY: 29750 AN XY: 113244

Gnomad AFR exome AF: 0.299

Gnomad AMR exome AF: 0.251

Gnomad ASJ exome AF: 0.197

Gnomad EAS exome AF: 0.315

Gnomad SAS exome AF: 0.258

Gnomad FIN exome AF: 0.315

Gnomad NFE exome AF: 0.251

Gnomad OTH exome AF: 0.231

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.306 AC: 415445 AN: 1355624 Hom.: 5 Cov.: 83 AF XY: 0.309 AC XY: 208690 AN XY: 675718

Gnomad4 AFR exome AF: 0.334

Gnomad4 AMR exome AF: 0.357

Gnomad4 ASJ exome AF: 0.301

Gnomad4 EAS exome AF: 0.366

Gnomad4 SAS exome AF: 0.337

Gnomad4 FIN exome AF: 0.374

Gnomad4 NFE exome AF: 0.296

Gnomad4 OTH exome AF: 0.312

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.299 AC: 39829 AN: 133042 Hom.: 4 Cov.: 43 AF XY: 0.306 AC XY: 19877 AN XY: 64958

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.283

Alfa AF: 0.238 Hom.: 1405

ExAC AF: 0.342 AC: 41455

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency (no homozygotes in ExAC) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.0010
DANN	Benign	0.085
DEOGEN2	Benign	0.0045	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0016	N
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.0047	T;T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.66	N;N
REVEL	Benign	0.0040
Sift	Benign	1.0	T;T
Sift4G	Benign	0.33	T;T
Polyphen		0.015	B;B
Vest4		0.10
MPC		0.0071
ClinPred		0.00037	T
GERP RS		-3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.025
gMVP		0.035

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0017
dbscSNV1_RF	Benign	0.25
SpliceAI score (max)		0.070		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: COSV62261499;