4-143999443-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002100.6(GYPB):​c.143C>A​(p.Thr48Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000199 in 1,507,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034067392).

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>A	p.Thr48Lys	missense	Exon 3 of 5	NP_002091.4
	GYPB	NM_001304382.1		c.65C>A	p.Thr22Lys	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>A	p.Thr48Lys	missense	Exon 3 of 5	ENSP00000427690.1
	GYPB	ENST00000506516.6	TSL:1	c.65C>A	p.Thr22Lys	missense	Exon 4 of 6	ENSP00000424025.2
	GYPB	ENST00000429670.3	TSL:1	c.143C>A	p.Thr48Lys	missense	Exon 3 of 5	ENSP00000394200.2

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151114 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.37e-7 AC: 1 AN: 1356814 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 679438

African (AFR) AF: 0.00 AC: 0 AN: 29768

American (AMR) AF: 0.00 AC: 0 AN: 43096

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25352

East Asian (EAS) AF: 0.00 AC: 0 AN: 39062

South Asian (SAS) AF: 0.00 AC: 0 AN: 82152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5518

European-Non Finnish (NFE) AF: 9.78e-7 AC: 1 AN: 1022040

Other (OTH) AF: 0.00 AC: 0 AN: 56862

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151114 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73792

African (AFR) AF: 0.00 AC: 0 AN: 40552

American (AMR) AF: 0.000131 AC: 2 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67980

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 8072

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.038
DANN	Benign	0.36
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.97	T
PhyloP100		-4.1
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.020
Sift	Benign	1.0	T
Sift4G	Benign	0.39	T
Vest4		0.089
MutPred		0.36		Gain of ubiquitination at T48 (P = 0.0101)
MVP		0.014
MPC		0.0051
ClinPred		0.034	T
GERP RS		-3.3
Varity_R		0.033
gMVP		0.033
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;