4-143999443-G-A

Variant names:

• chr4-143999443-G-A
• rs7683365
• NM_002100.6:c.143C>T

Variant summary

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

The NM_002100.6(GYPB):​c.143C>T​(p.Thr48Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,495,004 control chromosomes in the GnomAD database, including 66,928 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (6563 hom., cov: 32)
  • Exomes 𝑓: 0.29 (60365 hom.)
• Consequence: GYPB NM_002100.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.15
• Publications: 36 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 (MetaRNN=0.0023570359).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002100.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPB	NM_002100.6	MANE Select	c.143C>T	p.Thr48Met	missense	Exon 3 of 5	NP_002091.4
	GYPB	NM_001304382.1		c.65C>T	p.Thr22Met	missense	Exon 4 of 6	NP_001291311.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPB	ENST00000502664.6	TSL:1 MANE Select	c.143C>T	p.Thr48Met	missense	Exon 3 of 5	ENSP00000427690.1
	GYPB	ENST00000506516.6	TSL:1	c.65C>T	p.Thr22Met	missense	Exon 4 of 6	ENSP00000424025.2
	GYPB	ENST00000429670.3	TSL:1	c.143C>T	p.Thr48Met	missense	Exon 3 of 5	ENSP00000394200.2

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41494 AN: 151064 Hom.: 6556 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.0416

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.372

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.292

GnomAD2 exomes AF: 0.308 AC: 72912 AN: 237040 AF XY: 0.313

Gnomad AFR exome AF: 0.202

Gnomad AMR exome AF: 0.358

Gnomad ASJ exome AF: 0.353

Gnomad EAS exome AF: 0.0378

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.328

Gnomad OTH exome AF: 0.320

GnomAD4 exome AF: 0.292 AC: 391865 AN: 1343826 Hom.: 60365 Cov.: 21 AF XY: 0.296 AC XY: 199130 AN XY: 673414

African (AFR) AF: 0.184 AC: 5456 AN: 29576

American (AMR) AF: 0.348 AC: 14949 AN: 42988

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 8744 AN: 25232

East Asian (EAS) AF: 0.0464 AC: 1810 AN: 39034

South Asian (SAS) AF: 0.346 AC: 28303 AN: 81834

European-Finnish (FIN) AF: 0.327 AC: 17259 AN: 52842

Middle Eastern (MID) AF: 0.372 AC: 2043 AN: 5498

European-Non Finnish (NFE) AF: 0.294 AC: 296939 AN: 1010382

Other (OTH) AF: 0.290 AC: 16362 AN: 56440

GnomAD4 genome AF: 0.275 AC: 41518 AN: 151178 Hom.: 6563 Cov.: 32 AF XY: 0.276 AC XY: 20428 AN XY: 73890

African (AFR) AF: 0.194 AC: 7873 AN: 40652

American (AMR) AF: 0.325 AC: 4949 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1201 AN: 3466

East Asian (EAS) AF: 0.0417 AC: 216 AN: 5182

South Asian (SAS) AF: 0.334 AC: 1608 AN: 4820

European-Finnish (FIN) AF: 0.329 AC: 3467 AN: 10544

Middle Eastern (MID) AF: 0.348 AC: 101 AN: 290

European-Non Finnish (NFE) AF: 0.314 AC: 21350 AN: 67958

Other (OTH) AF: 0.289 AC: 611 AN: 2112

Alfa AF: 0.299 Hom.: 8072

Bravo AF: 0.268

TwinsUK AF: 0.311 AC: 1155

ALSPAC AF: 0.318 AC: 1225

ESP6500AA AF: 0.193 AC: 843

ESP6500EA AF: 0.318 AC: 2738

ExAC AF: 0.302 AC: 36602

Asia WGS AF: 0.206 AC: 719 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.11
DANN	Benign	0.91
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0019	N
LIST_S2	Benign	0.31	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-0.91	T
PhyloP100		-4.1
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.014
Sift	Benign	0.14	T
Sift4G	Benign	0.23	T
Vest4		0.046
MPC		0.0054
ClinPred		0.010	T
GERP RS		-3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.012
gMVP		0.039
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7683365; hg19: chr4-144920596; COSMIC: COSV51635096; COSMIC: COSV51635096;