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

Variant summary

Our verdict is Benign. The variant received -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

Publications

11 publications found

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:

GUSBP5 (HGNC:):

GUSBP5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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

GnomAD2 exomes

AF:

0.310

AC:

68749

AN:

221634

AF XY:

0.316

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 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

African (AFR)

AF:

0.175

AC:

4061

AN:

23162

American (AMR)

AF:

0.347

AC:

13961

AN:

40250

Ashkenazi Jewish (ASJ)

AF:

0.344

AC:

7802

AN:

22656

East Asian (EAS)

AF:

0.0462

AC:

1733

AN:

37530

South Asian (SAS)

AF:

0.341

AC:

25004

AN:

73220

European-Finnish (FIN)

AF:

0.326

AC:

17033

AN:

52304

Middle Eastern (MID)

AF:

0.361

AC:

1726

AN:

4784

European-Non Finnish (NFE)

AF:

0.268

AC:

186370

AN:

696194

Other (OTH)

AF:

0.277

AC:

12401

AN:

44752

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

7688

15376

23064

30752

38440

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4338

8676

13014

17352

21690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.274

AC:

41431

AN:

151290

Hom.:

6532

Cov.:

AF XY:

0.276

AC XY:

20408

AN XY:

73966

show subpopulations

African (AFR)

AF:

0.191

AC:

7779

AN:

40700

American (AMR)

AF:

0.323

AC:

4929

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

1212

AN:

3472

East Asian (EAS)

AF:

0.0418

AC:

216

AN:

5172

South Asian (SAS)

AF:

0.334

AC:

1607

AN:

4816

European-Finnish (FIN)

AF:

0.328

AC:

3473

AN:

10586

Middle Eastern (MID)

AF:

0.340

AC:

100

AN:

294

European-Non Finnish (NFE)

AF:

0.314

AC:

21364

AN:

67980

Other (OTH)

AF:

0.289

AC:

609

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1462

2924

4387

5849

7311

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

438

876

1314

1752

2190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.35

PhyloP100

-0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over