Genetic Variant NM_002100.6:c.143C>G (chr4-143999443-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002100.6(GYPB):c.143C>G(p.Thr48Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000862 in 1,507,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000066 ( 0 hom. )

Consequence

GYPB
NM_002100.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.15

Publications

36 publications found

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:):

GUSBP5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.031746835).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002100.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPB	NM_002100.6	MANE Select	c.143C>G	p.Thr48Arg	missense	Exon 3 of 5	NP_002091.4
	GYPB	NM_001304382.1		c.65C>G	p.Thr22Arg	missense	Exon 4 of 6	NP_001291311.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GYPB	ENST00000502664.6	TSL:1 MANE Select	c.143C>G	p.Thr48Arg	missense	Exon 3 of 5	ENSP00000427690.1
GYPB	ENST00000506516.6	TSL:1	c.65C>G	p.Thr22Arg	missense	Exon 4 of 6	ENSP00000424025.2
GYPB	ENST00000429670.3	TSL:1	c.143C>G	p.Thr48Arg	missense	Exon 3 of 5	ENSP00000394200.2

Frequencies

GnomAD3 genomes

AF:

0.0000265

AC:

AN:

151112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000493

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000422

AC:

AN:

237040

AF XY:

0.00000780

show subpopulations

Gnomad AFR exome

AF:

0.0000706

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000663

AC:

AN:

1356806

Hom.:

Cov.:

AF XY:

0.00000736

AC XY:

AN XY:

679432

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29768

American (AMR)

AF:

0.00

AC:

AN:

43096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25352

East Asian (EAS)

AF:

0.00

AC:

AN:

39062

South Asian (SAS)

AF:

0.00

AC:

AN:

82152

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52964

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5518

European-Non Finnish (NFE)

AF:

0.00000881

AC:

AN:

1022032

Other (OTH)

AF:

0.00

AC:

AN:

56862

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000265

AC:

AN:

151112

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73792

show subpopulations

African (AFR)

AF:

0.0000493

AC:

AN:

40552

American (AMR)

AF:

0.00

AC:

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67980

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

8072

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.011

(source)

DANN

Benign

0.29

DEOGEN2

Benign

0.0065

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.00046

LIST_S2

Benign

0.23

M_CAP

Benign

0.00076

MetaRNN

Benign

0.032

MetaSVM

Benign

-0.98

PhyloP100

-4.1

PROVEAN

Benign

-1.5

REVEL

Benign

0.029

Sift

Benign

0.87

Sift4G

Benign

0.49

Vest4

0.098

MutPred

0.26

Gain of solvent accessibility (P = 0.0503)

MVP

0.014

MPC

0.0051

ClinPred

0.047

GERP RS

-3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.048

gMVP

0.020

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over