4-143997559-C-G

Variant names:

• chr4-143997559-C-G
• rs1132783
• NM_002100.6:c.251G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000429670.3(GYPB):​c.176-1G>C variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,577,614 control chromosomes in the GnomAD database, including 39,768 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (3082 hom., cov: 32)
  • Exomes 𝑓: 0.22 (36686 hom.)
• Consequence: GYPB ENST00000429670.3 splice_acceptor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 26 publications found

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]

GUSBP5 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.014).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000429670.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPB	NM_002100.6	MANE Select	c.251G>C	p.Ser84Thr	missense	Exon 4 of 5	NP_002091.4
	GYPB	NM_001304382.1		c.173G>C	p.Ser58Thr	missense	Exon 5 of 6	NP_001291311.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPB	ENST00000502664.6	TSL:1 MANE Select	c.251G>C	p.Ser84Thr	missense	Exon 4 of 5	ENSP00000427690.1
	GYPB	ENST00000506516.6	TSL:1	c.173G>C	p.Ser58Thr	missense	Exon 5 of 6	ENSP00000424025.2
	GYPB	ENST00000513128.5	TSL:1	c.152G>C	p.Ser51Thr	missense	Exon 3 of 4	ENSP00000425244.1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27495 AN: 150972 Hom.: 3079 Cov.: 32

Gnomad AFR AF: 0.0777

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.213

GnomAD2 exomes AF: 0.215 AC: 53871 AN: 250318 AF XY: 0.225

Gnomad AFR exome AF: 0.0730

Gnomad AMR exome AF: 0.134

Gnomad ASJ exome AF: 0.259

Gnomad EAS exome AF: 0.194

Gnomad FIN exome AF: 0.207

Gnomad NFE exome AF: 0.231

Gnomad OTH exome AF: 0.225

GnomAD4 exome AF: 0.219 AC: 312394 AN: 1426526 Hom.: 36686 Cov.: 26 AF XY: 0.223 AC XY: 159040 AN XY: 711860

African (AFR) AF: 0.0671 AC: 2137 AN: 31826

American (AMR) AF: 0.138 AC: 6165 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 6707 AN: 25820

East Asian (EAS) AF: 0.198 AC: 7789 AN: 39340

South Asian (SAS) AF: 0.322 AC: 27458 AN: 85404

European-Finnish (FIN) AF: 0.205 AC: 10928 AN: 53190

Middle Eastern (MID) AF: 0.263 AC: 1487 AN: 5654

European-Non Finnish (NFE) AF: 0.219 AC: 236632 AN: 1081696

Other (OTH) AF: 0.222 AC: 13091 AN: 58994

GnomAD4 genome AF: 0.182 AC: 27493 AN: 151088 Hom.: 3082 Cov.: 32 AF XY: 0.183 AC XY: 13541 AN XY: 73856

African (AFR) AF: 0.0776 AC: 3145 AN: 40536

American (AMR) AF: 0.162 AC: 2475 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 910 AN: 3468

East Asian (EAS) AF: 0.208 AC: 1077 AN: 5166

South Asian (SAS) AF: 0.322 AC: 1547 AN: 4808

European-Finnish (FIN) AF: 0.209 AC: 2209 AN: 10548

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15433 AN: 67988

Other (OTH) AF: 0.216 AC: 454 AN: 2098

Alfa AF: 0.224 Hom.: 3031

Bravo AF: 0.170

TwinsUK AF: 0.229 AC: 849

ALSPAC AF: 0.230 AC: 886

ESP6500AA AF: 0.0794 AC: 348

ESP6500EA AF: 0.228 AC: 1961

ExAC AF: 0.218 AC: 26402

Asia WGS AF: 0.250 AC: 867 AN: 3476

EpiCase AF: 0.226

EpiControl AF: 0.232

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.90	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.1
DANN	Benign	0.44
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0065	N
PhyloP100		-1.3
ClinPred		0.0040	T
GERP RS		-4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.048
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1132783; hg19: chr4-144918712; COSMIC: COSV51621478; COSMIC: COSV51621478;