Variant rs1132783 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000429670.3(GYPB):c.176-1G>C variant causes a splice acceptor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,577,614 control chromosomes in the GnomAD database, including 39,768 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 3082 hom., cov: 32)

Exomes 𝑓: 0.22 ( 36686 hom. )

Consequence

GYPB
ENST00000429670.3 splice_acceptor

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.26

Variant links:

Genes affected

GYPB (HGNC:4703): (glycophorin B (MNS blood group)) Glycophorins A (GYPA) and B (GYPB) are major sialoglycoproteins of the human erythrocyte membrane which bear the antigenic determinants for the MN and Ss blood groups. GYPB gene consists of 5 exons and has 97% sequence homology with GYPA from the 5' UTR to the coding sequence encoding the first 45 amino acids. In addition to the M or N and S or s antigens, that commonly occur in all populations, about 40 related variant phenotypes have been identified. These variants include all the variants of the Miltenberger complex and several isoforms of Sta; also, Dantu, Sat, He, Mg, and deletion variants Ena, S-s-U- and Mk. Most of the variants are the result of gene recombinations between GYPA and GYPB. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

GYPB links:

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

GUSBP5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_addAF=-0.900358).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GYPB	NM_002100.6 linkuse as main transcript	c.251G>C	p.Ser84Thr	missense_variant	4/5	ENST00000502664.6
GYPB	XM_011531903.3 linkuse as main transcript	c.251G>C	p.Ser84Thr	missense_variant	4/5
GYPB	XM_011531904.4 linkuse as main transcript	c.224G>C	p.Ser75Thr	missense_variant	5/6
GYPB	NM_001304382.1 linkuse as main transcript	c.173G>C	p.Thr58=	synonymous_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GYPB	ENST00000502664.6 linkuse as main transcript	c.251G>C	p.Ser84Thr	missense_variant	4/5	1	NM_002100.6	A2	P06028-1

Frequencies

GnomAD3 genomes

AF:

0.182

AC:

27495

AN:

150972

Hom.:

3079

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0777

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.163

Gnomad ASJ

AF:

0.262

Gnomad EAS

AF:

0.209

Gnomad SAS

AF:

0.321

Gnomad FIN

AF:

0.209

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.213

GnomAD3 exomes

AF:

0.215

AC:

53871

AN:

250318

Hom.:

6491

AF XY:

0.225

AC XY:

30489

AN XY:

135512

show subpopulations

Gnomad AFR exome

AF:

0.0730

Gnomad AMR exome

AF:

0.134

Gnomad ASJ exome

AF:

0.259

Gnomad EAS exome

AF:

0.194

Gnomad SAS exome

AF:

0.324

Gnomad FIN exome

AF:

0.207

Gnomad NFE exome

AF:

0.231

Gnomad OTH exome

AF:

0.225

GnomAD4 exome

AF:

0.219

AC:

312394

AN:

1426526

Hom.:

36686

Cov.:

AF XY:

0.223

AC XY:

159040

AN XY:

711860

show subpopulations

Gnomad4 AFR exome

AF:

0.0671

Gnomad4 AMR exome

AF:

0.138

Gnomad4 ASJ exome

AF:

0.260

Gnomad4 EAS exome

AF:

0.198

Gnomad4 SAS exome

AF:

0.322

Gnomad4 FIN exome

AF:

0.205

Gnomad4 NFE exome

AF:

0.219

Gnomad4 OTH exome

AF:

0.222

GnomAD4 genome

AF:

0.182

AC:

27493

AN:

151088

Hom.:

3082

Cov.:

AF XY:

0.183

AC XY:

13541

AN XY:

73856

show subpopulations

Gnomad4 AFR

AF:

0.0776

Gnomad4 AMR

AF:

0.162

Gnomad4 ASJ

AF:

0.262

Gnomad4 EAS

AF:

0.208

Gnomad4 SAS

AF:

0.322

Gnomad4 FIN

AF:

0.209

Gnomad4 NFE

AF:

0.227

Gnomad4 OTH

AF:

0.216

Alfa

AF:

0.224

Hom.:

3031

Bravo

AF:

0.170

TwinsUK

AF:

0.229

AC:

849

ALSPAC

AF:

0.230

AC:

886

ESP6500AA

AF:

0.0794

AC:

348

ESP6500EA

AF:

0.228

AC:

1961

ExAC

AF:

0.218

AC:

26402

Asia WGS

AF:

0.250

AC:

867

AN:

3476

EpiCase

AF:

0.226

EpiControl

AF:

0.232

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.90

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.1

DANN

Benign

0.44

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0065

MutationTaster

Benign

1.0

P;P;P;P

ClinPred

0.0040

GERP RS

-4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over