4-144001245-C-T

Position:

chr4-144001245-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002100.6(GYPB):c.76G>A(p.Ala26Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,612,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

GYPB
NM_002100.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.726

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:

GYPB (HGNC:):

GYPB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.092273414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GYPB	NM_002100.6 linkuse as main transcript	c.76G>A	p.Ala26Thr	missense_variant	2/5	ENST00000502664.6	NP_002091.4	P06028-1
GYPB	XM_011531903.3 linkuse as main transcript	c.76G>A	p.Ala26Thr	missense_variant	2/5		XP_011530205.1
GYPB	XM_011531904.4 linkuse as main transcript	c.49G>A	p.Ala17Thr	missense_variant	3/6		XP_011530206.1
GYPB	NM_001304382.1 linkuse as main transcript	c.-3G>A		5_prime_UTR_variant	3/6		NP_001291311.1	P06028

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GYPB	ENST00000502664.6 linkuse as main transcript	c.76G>A	p.Ala26Thr	missense_variant	2/5	1	NM_002100.6	ENSP00000427690.1	P06028-1
GYPB	ENST00000504951.6 linkuse as main transcript	n.*62G>A		non_coding_transcript_exon_variant	3/7	1		ENSP00000421974.2	D6RA87
GYPB	ENST00000504951.6 linkuse as main transcript	n.*62G>A		3_prime_UTR_variant	3/7	1		ENSP00000421974.2	D6RA87

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151368

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

250996

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135666

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461302

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726970

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151368

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73930

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2022

The c.76G>A (p.A26T) alteration is located in exon 2 (coding exon 2) of the GYPB gene. This alteration results from a G to A substitution at nucleotide position 76, causing the alanine (A) at amino acid position 26 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.56

DANN

Benign

0.83

DEOGEN2

Benign

0.0055

.;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0045

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.0011

MetaRNN

Benign

0.092

T;T;T

MetaSVM

Benign

-1.1

PROVEAN

Uncertain

-3.5

D;N;.

REVEL

Benign

0.017

Sift

Uncertain

0.012

D;D;.

Sift4G

Uncertain

0.019

D;D;.

Vest4

0.035

MutPred

0.36

Loss of glycosylation at T23 (P = 0.0184);Loss of glycosylation at T23 (P = 0.0184);Loss of glycosylation at T23 (P = 0.0184);

MVP

0.014

MPC

0.0068

ClinPred

0.092

GERP RS

-3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.075

gMVP

0.026

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over