rs12499907

chr4-143999748-A-Cchr4-143999748-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002100.6(GYPB):c.137-299T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 151,162 control chromosomes in the GnomAD database, including 6,666 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 (6666 hom., cov: 32)
• Consequence: GYPB NM_002100.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.808

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:42319): (GUSB pseudogene 5)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• 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/exons	MANE	UniProt
GYPB	NM_002100.6	c.137-299T>G		intron_variant		ENST00000502664.6
GYPB	NM_001304382.1	c.59-299T>G		intron_variant
GYPB	XM_011531903.3	c.137-299T>G		intron_variant
GYPB	XM_011531904.4	c.110-299T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GYPB	ENST00000502664.6	c.137-299T>G		intron_variant		1	NM_002100.6	A2

Frequencies

GnomAD3 genomes AF: 0.278 AC: 41950 AN: 151046 Hom.: 6660 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.0425

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.278 AC: 41977 AN: 151162 Hom.: 6666 Cov.: 32 AF XY: 0.279 AC XY: 20590 AN XY: 73852

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.0425

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.286

Alfa AF: 0.185 Hom.: 410

Bravo AF: 0.273

Asia WGS AF: 0.203 AC: 711 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.3
Dann	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs12499907; hg19: chr4-144920901;