chr4-143999748-A-C

Variant names:

• chr4-143999748-A-C
• rs12499907
• NM_002100.6:c.137-299T>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.137-299T>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
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.317 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.137-299T>G		intron	N/A	NP_002091.4
	GYPB	NM_001304382.1		c.59-299T>G		intron	N/A	NP_001291311.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPB	ENST00000502664.6	TSL:1 MANE Select	c.137-299T>G		intron	N/A	ENSP00000427690.1
	GYPB	ENST00000506516.6	TSL:1	c.59-299T>G		intron	N/A	ENSP00000424025.2
	GYPB	ENST00000429670.3	TSL:1	c.137-299T>G		intron	N/A	ENSP00000394200.2

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

African (AFR) AF: 0.206 AC: 8359 AN: 40670

American (AMR) AF: 0.324 AC: 4937 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1217 AN: 3466

East Asian (EAS) AF: 0.0425 AC: 221 AN: 5194

South Asian (SAS) AF: 0.314 AC: 1512 AN: 4812

European-Finnish (FIN) AF: 0.327 AC: 3451 AN: 10566

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

European-Non Finnish (NFE) AF: 0.316 AC: 21436 AN: 67920

Other (OTH) AF: 0.286 AC: 602 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.48
PhyloP100		-0.81
Mutation Taster		=100/0	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: rs12499907; hg19: chr4-144920901;