Genetic Variant NM_002100.6:c.175+84T>A (chr4-143999327-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.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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.83

Publications

8 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.175+84T>A	intron_variant	Intron 3 of 4	ENST00000502664.6	NP_002091.4	P06028-1
GYPB	NM_001304382.1 link	c.97+84T>A	intron_variant	Intron 4 of 5		NP_001291311.1	P06028
GYPB	XM_011531903.3 link	c.175+84T>A	intron_variant	Intron 3 of 4		XP_011530205.1
GYPB	XM_011531904.4 link	c.148+84T>A	intron_variant	Intron 4 of 5		XP_011530206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GYPB	ENST00000502664.6 link	c.175+84T>A		intron_variant	Intron 3 of 4	1	NM_002100.6	ENSP00000427690.1		P06028-1
GYPB	ENST00000504951.6 link	n.*254+84T>A		intron_variant	Intron 5 of 6	1		ENSP00000421974.2		D6RA87

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41439

AN:

151364

Hom.:

6543

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:

0.327

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.:

AF XY:

0.305

AC XY:

94846

AN XY:

311208

show subpopulations

African (AFR)

AF:

0.192

AC:

2643

AN:

13768

American (AMR)

AF:

0.349

AC:

9656

AN:

27700

Ashkenazi Jewish (ASJ)

AF:

0.353

AC:

6807

AN:

19292

East Asian (EAS)

AF:

0.0477

AC:

1562

AN:

32744

South Asian (SAS)

AF:

0.353

AC:

20429

AN:

57924

European-Finnish (FIN)

AF:

0.325

AC:

16145

AN:

49636

Middle Eastern (MID)

AF:

0.370

AC:

1476

AN:

3988

European-Non Finnish (NFE)

AF:

0.310

AC:

105496

AN:

340732

Other (OTH)

AF:

0.298

AC:

9092

AN:

30552

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

5453

10907

16360

21814

27267

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

754

1508

2262

3016

3770

<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:

41464

AN:

151480

Hom.:

6550

Cov.:

AF XY:

0.276

AC XY:

20407

AN XY:

74060

show subpopulations

African (AFR)

AF:

0.191

AC:

7820

AN:

40870

American (AMR)

AF:

0.324

AC:

4939

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

1209

AN:

3466

East Asian (EAS)

AF:

0.0418

AC:

217

AN:

5192

South Asian (SAS)

AF:

0.333

AC:

1604

AN:

4814

European-Finnish (FIN)

AF:

0.327

AC:

3463

AN:

10578

Middle Eastern (MID)

AF:

0.340

AC:

100

AN:

294

European-Non Finnish (NFE)

AF:

0.314

AC:

21363

AN:

67992

Other (OTH)

AF:

0.288

AC:

607

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1517

3033

4550

6066

7583

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:

0.294

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

(source)

DANN

Benign

0.31

PhyloP100

-1.8

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