4-143880518-A-C

Variant names:

• chr4-143880518-A-C
• rs146400730
• NM_198682.3:c.38-9T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_198682.3(GYPE):​c.38-9T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (0 hom., cov: 39)
  • Exomes 𝑓: 0.31 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: GYPE NM_198682.3 intron
• Scores: Splicing: ADA: 0.09328
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0830

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 (BayesDel_noAF=-0.83).
• BP6: Variant 4-143880518-A-C is Benign according to our data. Variant chr4-143880518-A-C is described in ClinVar as [Benign]. Clinvar id is 769294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYPE	NM_198682.3	c.38-9T>G		intron_variant	Intron 1 of 3	ENST00000358615.9	NP_941391.2
GYPE	NM_002102.4	c.38-9T>G		intron_variant	Intron 1 of 3		NP_002093.2
LOC105377459	XR_001741861.1	n.1463+14442A>C		intron_variant	Intron 9 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GYPE	ENST00000358615.9	c.38-9T>G		intron_variant	Intron 1 of 3	1	NM_198682.3	ENSP00000351430.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 27596 AN: 120544 Hom.: 0 Cov.: 39 FAILED QC

Gnomad AFR AF: 0.0590

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.212

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.306 AC: 341356 AN: 1115072 Hom.: 1 Cov.: 74 AF XY: 0.309 AC XY: 172735 AN XY: 559014

Gnomad4 AFR exome AF: 0.0565

Gnomad4 AMR exome AF: 0.360

Gnomad4 ASJ exome AF: 0.293

Gnomad4 EAS exome AF: 0.302

Gnomad4 SAS exome AF: 0.346

Gnomad4 FIN exome AF: 0.398

Gnomad4 NFE exome AF: 0.306

Gnomad4 OTH exome AF: 0.299

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.229 AC: 27607 AN: 120662 Hom.: 0 Cov.: 39 AF XY: 0.236 AC XY: 13945 AN XY: 59188

Gnomad4 AFR AF: 0.0590

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.211

Alfa AF: 0.304 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 20, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.7
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.093
dbscSNV1_RF	Benign	0.37
SpliceAI score (max)		0.010		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: rs146400730; hg19: chr4-144801671; COSMIC: COSV62261299;