rs1132785

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

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. 17/23 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 (★★).

• 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, multiple submitters, no conflicts B:2
• 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=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 VariationId is 402918.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.38G>C	p.Gly13Ala	missense_variant, splice_region_variant	Exon 2 of 4	ENST00000358615.9	NP_941391.2
GYPE	NM_002102.4	c.38G>C	p.Gly13Ala	missense_variant, splice_region_variant	Exon 2 of 4		NP_002093.2
LOC105377459	XR_001741861.1	n.1463+14433C>G		intron_variant	Intron 9 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GYPE	ENST00000358615.9	c.38G>C	p.Gly13Ala	missense_variant, splice_region_variant	Exon 2 of 4	1	NM_198682.3	ENSP00000351430.4

Frequencies

GnomAD3 genomes AF: 0.299 AC: 39796 AN: 132948 Hom.: 4 Cov.: 43

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

GnomAD2 exomes AF: 0.262 AC: 54614 AN: 208744 AF XY: 0.263

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.334 AC: 10114 AN: 30252

American (AMR) AF: 0.357 AC: 14973 AN: 41988

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 7367 AN: 24436

East Asian (EAS) AF: 0.366 AC: 12785 AN: 34920

South Asian (SAS) AF: 0.337 AC: 26835 AN: 79640

European-Finnish (FIN) AF: 0.374 AC: 18974 AN: 50754

Middle Eastern (MID) AF: 0.330 AC: 1803 AN: 5468

European-Non Finnish (NFE) AF: 0.296 AC: 305220 AN: 1032452

Other (OTH) AF: 0.312 AC: 17374 AN: 55714

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.306 AC: 10626 AN: 34696

American (AMR) AF: 0.302 AC: 4100 AN: 13560

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 865 AN: 3056

East Asian (EAS) AF: 0.347 AC: 1504 AN: 4334

South Asian (SAS) AF: 0.327 AC: 1405 AN: 4300

European-Finnish (FIN) AF: 0.341 AC: 3214 AN: 9414

Middle Eastern (MID) AF: 0.335 AC: 83 AN: 248

European-Non Finnish (NFE) AF: 0.284 AC: 17282 AN: 60782

Other (OTH) AF: 0.283 AC: 530 AN: 1874

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.238 Hom.: 1405

ExAC AF: 0.342 AC: 41455

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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) -

not provided Benign:1

-

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
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
LIST_S2	Benign	0.48	.;T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.0047	T;T
MetaSVM	Benign	-0.94	T
PhyloP100		-2.4
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
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs1132785; hg19: chr4-144801662; COSMIC: COSV62261499;