chr4-143997622-A-G

Position:

chr4-143997622-A-G

Variant summary

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

The NM_002100.6(GYPB):c.188T>C(p.Ile63Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,417,182 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GYPB
NM_002100.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0600

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 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=0.106919944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GYPB	NM_002100.6 link	c.188T>C	p.Ile63Thr	missense_variant	4/5	ENST00000502664.6	NP_002091.4	P06028-1
GYPB	NM_001304382.1 link	c.110T>C	p.Ile37Thr	missense_variant	5/6		NP_001291311.1	P06028
GYPB	XM_011531903.3 link	c.188T>C	p.Ile63Thr	missense_variant	4/5		XP_011530205.1
GYPB	XM_011531904.4 link	c.161T>C	p.Ile54Thr	missense_variant	5/6		XP_011530206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GYPB	ENST00000502664.6 link	c.188T>C	p.Ile63Thr	missense_variant	4/5	1	NM_002100.6	ENSP00000427690.1	P06028-1
GYPB	ENST00000504951.6 link	n.*267T>C		non_coding_transcript_exon_variant	6/7	1		ENSP00000421974.2	D6RA87
GYPB	ENST00000504951.6 link	n.*267T>C		3_prime_UTR_variant	6/7	1		ENSP00000421974.2	D6RA87

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000800

AC:

AN:

249850

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135408

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1417182

Hom.:

Cov.:

AF XY:

0.00000282

AC XY:

AN XY:

708252

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:

0.00000186

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Nov 15, 2024

The c.188T>C (p.I63T) alteration is located in exon 4 (coding exon 4) of the GYPB gene. This alteration results from a T to C substitution at nucleotide position 188, causing the isoleucine (I) at amino acid position 63 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

0.34

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.61

CADD

Benign

7.9

DANN

Benign

0.57

DEOGEN2

Benign

0.017

T;.;.;.

Eigen

Benign

-0.91

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0088

LIST_S2

Benign

0.50

T;T;T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

-2.3

N;D;.;.

REVEL

Benign

0.083

Sift

Uncertain

0.0060

D;D;.;.

Sift4G

Uncertain

0.020

D;D;.;.

Vest4

0.31

MVP

0.040

MPC

0.0052

ClinPred

0.16

GERP RS

-0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.12

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