4-144001260-T-G

Position:

chr4-144001260-T-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002100.6(GYPB):c.61A>C(p.Ser21Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,612,980 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00020 ( 2 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

GYPB
NM_002100.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.950

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.051583707).

BS2

High Homozygotes in GnomAd4 at 2 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GYPB	NM_002100.6 linkuse as main transcript	c.61A>C	p.Ser21Arg	missense_variant	2/5	ENST00000502664.6	NP_002091.4	P06028-1
GYPB	XM_011531903.3 linkuse as main transcript	c.61A>C	p.Ser21Arg	missense_variant	2/5		XP_011530205.1
GYPB	XM_011531904.4 linkuse as main transcript	c.34A>C	p.Ser12Arg	missense_variant	3/6		XP_011530206.1
GYPB	NM_001304382.1 linkuse as main transcript	c.-18A>C		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.61A>C	p.Ser21Arg	missense_variant	2/5	1	NM_002100.6	ENSP00000427690.1	P06028-1
GYPB	ENST00000504951.6 linkuse as main transcript	n.*47A>C		non_coding_transcript_exon_variant	3/7	1		ENSP00000421974.2	D6RA87
GYPB	ENST00000504951.6 linkuse as main transcript	n.*47A>C		3_prime_UTR_variant	3/7	1		ENSP00000421974.2	D6RA87

Frequencies

GnomAD3 genomes

AF:

0.000198

AC:

AN:

151558

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000686

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000837

AC:

AN:

250968

Hom.:

AF XY:

0.0000663

AC XY:

AN XY:

135658

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.0000289

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1461304

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726966

show subpopulations

Gnomad4 AFR exome

AF:

0.000662

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000198

AC:

AN:

151676

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74184

show subpopulations

Gnomad4 AFR

AF:

0.000684

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000419

Hom.:

Bravo

AF:

0.000264

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

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

Oct 03, 2024

The c.61A>C (p.S21R) alteration is located in exon 2 (coding exon 2) of the GYPB gene. This alteration results from a A to C substitution at nucleotide position 61, causing the serine (S) at amino acid position 21 to be replaced by an arginine (R). 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

Uncertain

0.47

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.59

CADD

Benign

7.7

DANN

Uncertain

0.99

DEOGEN2

Benign

0.050

.;T;.

Eigen

Benign

-0.71

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0047

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.0015

MetaRNN

Benign

0.052

T;T;T

MetaSVM

Benign

-1.0

PROVEAN

Pathogenic

-4.8

D;D;.

REVEL

Benign

0.029

Sift

Uncertain

0.0020

D;D;.

Sift4G

Pathogenic

0.0

D;D;.

Vest4

0.093

MutPred

0.38

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

0.040

MPC

0.022

ClinPred

0.22

GERP RS

-3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.19

gMVP

0.037

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