rs7661933

chr4-143999327-A-T

Variant summary

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

The NM_002100.6(GYPB):c.175+84T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 727,816 control chromosomes in the GnomAD database, including 34,824 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 0.27 (6550 hom., cov: 32)
  • Exomes 𝑓: 0.30 (28274 hom.)
• Consequence: GYPB NM_002100.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83

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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GYPB	NM_002100.6	c.175+84T>A		intron_variant		ENST00000502664.6
GYPB	NM_001304382.1	c.97+84T>A		intron_variant
GYPB	XM_011531903.3	c.175+84T>A		intron_variant
GYPB	XM_011531904.4	c.148+84T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GYPB	ENST00000502664.6	c.175+84T>A		intron_variant		1	NM_002100.6	A2

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41439 AN: 151364 Hom.: 6543 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.0417

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.301 AC: 173306 AN: 576336 Hom.: 28274 Cov.: 7 AF XY: 0.305 AC XY: 94846 AN XY: 311208

Gnomad4 AFR exome AF: 0.192

Gnomad4 AMR exome AF: 0.349

Gnomad4 ASJ exome AF: 0.353

Gnomad4 EAS exome AF: 0.0477

Gnomad4 SAS exome AF: 0.353

Gnomad4 FIN exome AF: 0.325

Gnomad4 NFE exome AF: 0.310

Gnomad4 OTH exome AF: 0.298

GnomAD4 genome AF: 0.274 AC: 41464 AN: 151480 Hom.: 6550 Cov.: 32 AF XY: 0.276 AC XY: 20407 AN XY: 74060

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.0418

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.288

Alfa AF: 0.294 Hom.: 876

Bravo AF: 0.268

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.11
Dann	Benign	0.31

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: rs7661933; hg19: chr4-144920480;