4-143997550-C-T

Position:

• chr4-143997550-C-T

Variant summary

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

The NM_002100.6(GYPB):​c.260G>A​(p.Arg87Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000527 in 1,571,680 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (15 hom., cov: 32)
  • Exomes 𝑓: 0.00034 (14 hom.)
• Consequence: GYPB NM_002100.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.63

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 (MetaRNN=0.0048134327).
• BP6: Variant 4-143997550-C-T is Benign according to our data. Variant chr4-143997550-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3388670.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 15 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GYPB	NM_002100.6	c.260G>A	p.Arg87Gln	missense_variant	4/5	ENST00000502664.6	NP_002091.4
GYPB	NM_001304382.1	c.182G>A	p.Arg61Gln	missense_variant	5/6		NP_001291311.1
GYPB	XM_011531903.3	c.260G>A	p.Arg87Gln	missense_variant	4/5		XP_011530205.1
GYPB	XM_011531904.4	c.233G>A	p.Arg78Gln	missense_variant	5/6		XP_011530206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GYPB	ENST00000502664.6	c.260G>A	p.Arg87Gln	missense_variant	4/5	1	NM_002100.6	ENSP00000427690.1
GYPB	ENST00000504951.6	n.*339G>A		non_coding_transcript_exon_variant	6/7	1		ENSP00000421974.2
GYPB	ENST00000504951.6	n.*339G>A		3_prime_UTR_variant	6/7	1		ENSP00000421974.2

Frequencies

GnomAD3 genomes AF: 0.00224 AC: 339 AN: 151112 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.00793

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.000703 AC: 176 AN: 250306 Hom.: 5 AF XY: 0.000598 AC XY: 81 AN XY: 135544

Gnomad AFR exome AF: 0.00929

Gnomad AMR exome AF: 0.000319

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000654

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.000494

GnomAD4 exome AF: 0.000343 AC: 487 AN: 1420452 Hom.: 14 Cov.: 25 AF XY: 0.000319 AC XY: 226 AN XY: 709494

Gnomad4 AFR exome AF: 0.00722

Gnomad4 AMR exome AF: 0.000269

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00373

Gnomad4 SAS exome AF: 0.0000235

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000548

Gnomad4 OTH exome AF: 0.000646

GnomAD4 genome AF: 0.00226 AC: 342 AN: 151228 Hom.: 15 Cov.: 32 AF XY: 0.00222 AC XY: 164 AN XY: 73942

Gnomad4 AFR AF: 0.00798

Gnomad4 AMR AF: 0.000589

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000967

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00143

Alfa AF: 0.00138 Hom.: 5

ESP6500AA AF: 0.0114 AC: 50

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000923 AC: 112

Asia WGS AF: 0.00231 AC: 8 AN: 3476

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

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: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.66
DANN	Benign	0.90
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.012
Sift	Benign	0.043	D
Sift4G	Uncertain	0.031	D
Vest4		0.20
MVP		0.040
ClinPred		0.028	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)		0.070		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: rs112711627; hg19: chr4-144918703; COSMIC: COSV99302694; COSMIC: COSV99302694;