dbSNP rs7683365: GYPB:p.Thr48Met (chr4-143999443-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002100.6(GYPB):c.143C>T(p.Thr48Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,495,004 control chromosomes in the GnomAD database, including 66,928 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.27 ( 6563 hom., cov: 32)

Exomes 𝑓: 0.29 ( 60365 hom. )

Consequence

GYPB
NM_002100.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.15

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:

ENSG00000251600 (HGNC:):

ENSG00000251600 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 (MetaRNN=0.0023570359).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYPB	NM_002100.6 link	c.143C>T	p.Thr48Met	missense_variant	Exon 3 of 5	ENST00000502664.6	NP_002091.4	P06028-1
GYPB	NM_001304382.1 link	c.65C>T	p.Thr22Met	missense_variant	Exon 4 of 6		NP_001291311.1	P06028
GYPB	XM_011531903.3 link	c.143C>T	p.Thr48Met	missense_variant	Exon 3 of 5		XP_011530205.1
GYPB	XM_011531904.4 link	c.116C>T	p.Thr39Met	missense_variant	Exon 4 of 6		XP_011530206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GYPB	ENST00000502664.6 link	c.143C>T	p.Thr48Met	missense_variant	Exon 3 of 5	1	NM_002100.6	ENSP00000427690.1	P06028-1
GYPB	ENST00000504951.6 link	n.*222C>T		non_coding_transcript_exon_variant	Exon 5 of 7	1		ENSP00000421974.2	D6RA87
GYPB	ENST00000504951.6 link	n.*222C>T		3_prime_UTR_variant	Exon 5 of 7	1		ENSP00000421974.2	D6RA87

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

41494

AN:

151064

Hom.:

6556

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.324

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.0416

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.329

Gnomad MID

AF:

0.372

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.292

GnomAD3 exomes

AF:

0.308

AC:

72912

AN:

237040

Hom.:

12087

AF XY:

0.313

AC XY:

40189

AN XY:

128196

show subpopulations

Gnomad AFR exome

AF:

0.202

Gnomad AMR exome

AF:

0.358

Gnomad ASJ exome

AF:

0.353

Gnomad EAS exome

AF:

0.0378

Gnomad SAS exome

AF:

0.357

Gnomad FIN exome

AF:

0.333

Gnomad NFE exome

AF:

0.328

Gnomad OTH exome

AF:

0.320

GnomAD4 exome

AF:

0.292

AC:

391865

AN:

1343826

Hom.:

60365

Cov.:

AF XY:

0.296

AC XY:

199130

AN XY:

673414

show subpopulations

Gnomad4 AFR exome

AF:

0.184

Gnomad4 AMR exome

AF:

0.348

Gnomad4 ASJ exome

AF:

0.347

Gnomad4 EAS exome

AF:

0.0464

Gnomad4 SAS exome

AF:

0.346

Gnomad4 FIN exome

AF:

0.327

Gnomad4 NFE exome

AF:

0.294

Gnomad4 OTH exome

AF:

0.290

GnomAD4 genome

AF:

0.275

AC:

41518

AN:

151178

Hom.:

6563

Cov.:

AF XY:

0.276

AC XY:

20428

AN XY:

73890

show subpopulations

Gnomad4 AFR

AF:

0.194

Gnomad4 AMR

AF:

0.325

Gnomad4 ASJ

AF:

0.347

Gnomad4 EAS

AF:

0.0417

Gnomad4 SAS

AF:

0.334

Gnomad4 FIN

AF:

0.329

Gnomad4 NFE

AF:

0.314

Gnomad4 OTH

AF:

0.289

Alfa

AF:

0.299

Hom.:

4971

Bravo

AF:

0.268

TwinsUK

AF:

0.311

AC:

1155

ALSPAC

AF:

0.318

AC:

1225

ESP6500AA

AF:

0.193

AC:

843

ESP6500EA

AF:

0.318

AC:

2738

ExAC

AF:

0.302

AC:

36602

Asia WGS

AF:

0.206

AC:

719

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.11

DANN

Benign

0.91

DEOGEN2

Benign

0.0057

.;T;.;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.31

T;T;T;T;T

MetaRNN

Benign

0.0024

T;T;T;T;T

MetaSVM

Benign

-0.91

PROVEAN

Benign

-1.1

N;N;N;.;.

REVEL

Benign

0.014

Sift

Benign

0.14

T;T;T;.;.

Sift4G

Benign

0.23

T;T;T;.;.

Vest4

0.046

MPC

0.0054

ClinPred

0.010

GERP RS

-3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.012

gMVP

0.039

Splicing

Name

Calibrated prediction

Score

Prediction

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

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