rs12499906

Variant names:

• chr4-143999732-A-C
• rs12499906
• NM_002100.6:c.137-283T>G

Variant summary

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

The NM_002100.6(GYPB):​c.137-283T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 151,196 control chromosomes in the GnomAD database, including 6,612 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6612 hom., cov: 32)
• Consequence: GYPB NM_002100.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64
• Publications: 4 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 (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYPB	NM_002100.6	c.137-283T>G		intron_variant	Intron 2 of 4	ENST00000502664.6	NP_002091.4
GYPB	NM_001304382.1	c.59-283T>G		intron_variant	Intron 3 of 5		NP_001291311.1
GYPB	XM_011531903.3	c.137-283T>G		intron_variant	Intron 2 of 4		XP_011530205.1
GYPB	XM_011531904.4	c.110-283T>G		intron_variant	Intron 3 of 5		XP_011530206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GYPB	ENST00000502664.6	c.137-283T>G		intron_variant	Intron 2 of 4	1	NM_002100.6	ENSP00000427690.1
GYPB	ENST00000504951.6	n.*216-283T>G		intron_variant	Intron 4 of 6	1		ENSP00000421974.2

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41771 AN: 151080 Hom.: 6606 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.0413

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.290

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.276 AC: 41798 AN: 151196 Hom.: 6612 Cov.: 32 AF XY: 0.277 AC XY: 20496 AN XY: 73870

African (AFR) AF: 0.202 AC: 8230 AN: 40652

American (AMR) AF: 0.324 AC: 4944 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1217 AN: 3468

East Asian (EAS) AF: 0.0414 AC: 215 AN: 5188

South Asian (SAS) AF: 0.313 AC: 1503 AN: 4808

European-Finnish (FIN) AF: 0.326 AC: 3447 AN: 10558

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21394 AN: 67952

Other (OTH) AF: 0.287 AC: 606 AN: 2112

Alfa AF: 0.297 Hom.: 889

Bravo AF: 0.271

Asia WGS AF: 0.196 AC: 687 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs12499906; hg19: chr4-144920885;