4-143997560-T-C

Position:

• chr4-143997560-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000429670.3(GYPB):​c.176-2A>G variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000605 in 1,589,484 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00049 (10 hom.)
• Consequence: GYPB ENST00000429670.3 splice_acceptor, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.18

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.897846).
• BP6: Variant 4-143997560-T-C is Benign according to our data. Variant chr4-143997560-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3388470.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 9 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GYPB	NM_002100.6	c.250A>G	p.Ser84Gly	missense_variant	4/5	ENST00000502664.6	NP_002091.4
GYPB	NM_001304382.1	c.172A>G	p.Ser58Gly	missense_variant	5/6		NP_001291311.1
GYPB	XM_011531903.3	c.250A>G	p.Ser84Gly	missense_variant	4/5		XP_011530205.1
GYPB	XM_011531904.4	c.223A>G	p.Ser75Gly	missense_variant	5/6		XP_011530206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GYPB	ENST00000502664.6	c.250A>G	p.Ser84Gly	missense_variant	4/5	1	NM_002100.6	ENSP00000427690.1
GYPB	ENST00000504951.6	n.*329A>G		non_coding_transcript_exon_variant	6/7	1		ENSP00000421974.2
GYPB	ENST00000504951.6	n.*329A>G		3_prime_UTR_variant	6/7	1		ENSP00000421974.2

Frequencies

GnomAD3 genomes AF: 0.00169 AC: 256 AN: 151246 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00424

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.00288

GnomAD3 exomes AF: 0.000615 AC: 154 AN: 250396 Hom.: 2 AF XY: 0.000553 AC XY: 75 AN XY: 135558

Gnomad AFR exome AF: 0.00419

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000371

Gnomad OTH exome AF: 0.000329

GnomAD4 exome AF: 0.000490 AC: 705 AN: 1438122 Hom.: 10 Cov.: 27 AF XY: 0.000482 AC XY: 346 AN XY: 717200

Gnomad4 AFR exome AF: 0.00341

Gnomad4 AMR exome AF: 0.00125

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000507

Gnomad4 SAS exome AF: 0.0000350

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.000451

Gnomad4 OTH exome AF: 0.000673

GnomAD4 genome AF: 0.00169 AC: 256 AN: 151362 Hom.: 9 Cov.: 32 AF XY: 0.00143 AC XY: 106 AN XY: 74028

Gnomad4 AFR AF: 0.00423

Gnomad4 AMR AF: 0.00288

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000471

Gnomad4 OTH AF: 0.00285

Alfa AF: 0.000718 Hom.: 3

Bravo AF: 0.00213

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00616 AC: 27

ESP6500EA AF: 0.000930 AC: 8

ExAC AF: 0.000610 AC: 74

Asia WGS AF: 0.000578 AC: 2 AN: 3476

EpiCase AF: 0.000327

EpiControl AF: 0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

GYPB: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.90	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.022
DANN	Benign	0.43
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0034	N
M_CAP	Benign	0.00054	T
ClinPred		0.0032	T
GERP RS		-4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs184961047; hg19: chr4-144918713;