dbSNP rs3800695: BPGM:c.-61-656T>C (chr7-134660791-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001724.5(BPGM):c.-61-656T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,650 control chromosomes in the GnomAD database, including 1,538 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 0.13 ( 1535 hom., cov: 32)

Exomes 𝑓: 0.092 ( 3 hom. )

Consequence

BPGM
NM_001724.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.367

Publications

1 publications found

Variant links:

Genes affected

BPGM (HGNC:1093): (bisphosphoglycerate mutase) 2,3-diphosphoglycerate (2,3-DPG) is a small molecule found at high concentrations in red blood cells where it binds to and decreases the oxygen affinity of hemoglobin. This gene encodes a multifunctional enzyme that catalyzes 2,3-DPG synthesis via its synthetase activity, and 2,3-DPG degradation via its phosphatase activity. The enzyme also has phosphoglycerate phosphomutase activity. Deficiency of this enzyme increases the affinity of cells for oxygen. Mutations in this gene result in hemolytic anemia. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Sep 2009]

BPGM Gene-Disease associations (from GenCC):

hemolytic anemia due to diphosphoglycerate mutase deficiency
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)

BPGM links:

LOC124901750 (HGNC:):

LOC124901750 links:

Genome browser will be placed here

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=-0.82).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BPGM	NM_001724.5 link	c.-61-656T>C		intron_variant	Intron 1 of 2	ENST00000344924.8	NP_001715.1	P07738A0A024R782

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
BPGM	ENST00000344924.8 link	c.-61-656T>C	intron_variant	Intron 1 of 2	1	NM_001724.5	ENSP00000342032.3	P07738
BPGM	ENST00000393132.2 link	c.-61-656T>C	intron_variant	Intron 2 of 3	5		ENSP00000376840.2	P07738
BPGM	ENST00000418040.5 link	c.-61-656T>C	intron_variant	Intron 2 of 3	5		ENSP00000399838.1	P07738
BPGM	ENST00000443095.1 link	c.-62+31T>C	intron_variant	Intron 1 of 1	4		ENSP00000403050.1	C9JH23

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

20311

AN:

152084

Hom.:

1530

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.0673

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.173

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.142

GnomAD4 exome

AF:

0.0915

AC:

AN:

448

Hom.:

Cov.:

AF XY:

0.0820

AC XY:

AN XY:

244

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.139

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0906

AC:

AN:

342

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.134

AC:

20342

AN:

152202

Hom.:

1535

Cov.:

AF XY:

0.135

AC XY:

10067

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.159

AC:

6603

AN:

41526

American (AMR)

AF:

0.183

AC:

2803

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

370

AN:

3470

East Asian (EAS)

AF:

0.0671

AC:

348

AN:

5186

South Asian (SAS)

AF:

0.118

AC:

569

AN:

4818

European-Finnish (FIN)

AF:

0.173

AC:

1832

AN:

10574

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.109

AC:

7413

AN:

68012

Other (OTH)

AF:

0.143

AC:

302

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

896

1792

2689

3585

4481

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

226

452

678

904

1130

<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:

0.116

Hom.:

564

Bravo

AF:

0.136

Asia WGS

AF:

0.123

AC:

428

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.4

(source)

DANN

Benign

0.52

PhyloP100

-0.37

PromoterAI

-0.066

Neutral

(source)

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