dbSNP rs7662277: GYPB:c.137-36T>A (chr4-143999485-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002100.6(GYPB):c.137-36T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,146,142 control chromosomes in the GnomAD database, including 44,887 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 ( 6532 hom., cov: 32)

Exomes 𝑓: 0.27 ( 38355 hom. )

Consequence

GYPB
NM_002100.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.848

Variant links:

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]

GYPB links:

ENSG00000251600 (HGNC:):

ENSG00000251600 links:

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ACMG classification

Classification made for transcript

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	Effect	Exon rank	MANE	Protein	UniProt
GYPB	NM_002100.6 link	c.137-36T>A	intron_variant	Intron 2 of 4	ENST00000502664.6	NP_002091.4	P06028-1
GYPB	NM_001304382.1 link	c.59-36T>A	intron_variant	Intron 3 of 5		NP_001291311.1	P06028
GYPB	XM_011531903.3 link	c.137-36T>A	intron_variant	Intron 2 of 4		XP_011530205.1
GYPB	XM_011531904.4 link	c.110-36T>A	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 link	c.137-36T>A		intron_variant	Intron 2 of 4	1	NM_002100.6	ENSP00000427690.1		P06028-1
GYPB	ENST00000504951.6 link	n.*216-36T>A		intron_variant	Intron 4 of 6	1		ENSP00000421974.2		D6RA87

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41406

AN:

151174

Hom.:

6525

Cov.:

show subpopulations

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:

0.328

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.292

GnomAD3 exomes

AF:

0.310

AC:

68749

AN:

221634

Hom.:

11389

AF XY:

0.316

AC XY:

37793

AN XY:

119604

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.362

Gnomad ASJ exome

AF:

0.361

Gnomad EAS exome

AF:

0.0376

Gnomad SAS exome

AF:

0.361

Gnomad FIN exome

AF:

0.334

Gnomad NFE exome

AF:

0.331

Gnomad OTH exome

AF:

0.322

GnomAD4 exome

AF:

0.271

AC:

270091

AN:

994852

Hom.:

38355

Cov.:

AF XY:

0.278

AC XY:

142603

AN XY:

512914

show subpopulations

Gnomad4 AFR exome

AF:

0.175

Gnomad4 AMR exome

AF:

0.347

Gnomad4 ASJ exome

AF:

0.344

Gnomad4 EAS exome

AF:

0.0462

Gnomad4 SAS exome

AF:

0.341

Gnomad4 FIN exome

AF:

0.326

Gnomad4 NFE exome

AF:

0.268

Gnomad4 OTH exome

AF:

0.277

GnomAD4 genome

AF:

0.274

AC:

41431

AN:

151290

Hom.:

6532

Cov.:

AF XY:

0.276

AC XY:

20408

AN XY:

73966

show subpopulations

Gnomad4 AFR

AF:

0.191

Gnomad4 AMR

AF:

0.323

Gnomad4 ASJ

AF:

0.349

Gnomad4 EAS

AF:

0.0418

Gnomad4 SAS

AF:

0.334

Gnomad4 FIN

AF:

0.328

Gnomad4 NFE

AF:

0.314

Gnomad4 OTH

AF:

0.289

Alfa

AF:

0.305

Hom.:

1372

Bravo

AF:

0.268

Asia WGS

AF:

0.206

AC:

721

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.28

DANN

Benign

0.35

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over