rs145982146

Variant names:

• chr7-134661993-G-A
• rs145982146
• NM_001724.5:c.486G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001724.5(BPGM):​c.486G>A​(p.Leu162Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,614,154 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (1 hom.)
• Consequence: BPGM NM_001724.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.15
• Publications: 0 publications found

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, Labcorp Genetics (formerly Invitae), Ambry Genetics

LOC124901750 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 7-134661993-G-A is Benign according to our data. Variant chr7-134661993-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2759959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.15 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001724.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPGM	NM_001724.5	MANE Select	c.486G>A	p.Leu162Leu	synonymous	Exon 2 of 3	NP_001715.1	P07738
	BPGM	NM_001293085.2		c.486G>A	p.Leu162Leu	synonymous	Exon 3 of 4	NP_001280014.1	P07738
	BPGM	NM_199186.3		c.486G>A	p.Leu162Leu	synonymous	Exon 3 of 4	NP_954655.1	A0A024R782

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPGM	ENST00000344924.8	TSL:1 MANE Select	c.486G>A	p.Leu162Leu	synonymous	Exon 2 of 3	ENSP00000342032.3	P07738
	BPGM	ENST00000393132.2	TSL:5	c.486G>A	p.Leu162Leu	synonymous	Exon 3 of 4	ENSP00000376840.2	P07738
	BPGM	ENST00000418040.5	TSL:5	c.486G>A	p.Leu162Leu	synonymous	Exon 3 of 4	ENSP00000399838.1	P07738

Frequencies

GnomAD3 genomes AF: 0.00104 AC: 158 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00187

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000907 AC: 228 AN: 251374 AF XY: 0.000876

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000323

Gnomad NFE exome AF: 0.00171

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.00177 AC: 2582 AN: 1461866 Hom.: 1 Cov.: 31 AF XY: 0.00170 AC XY: 1233 AN XY: 727236

African (AFR) AF: 0.000179 AC: 6 AN: 33476

American (AMR) AF: 0.0000895 AC: 4 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000267 AC: 23 AN: 86258

European-Finnish (FIN) AF: 0.000262 AC: 14 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00221 AC: 2458 AN: 1112002

Other (OTH) AF: 0.00127 AC: 77 AN: 60396

GnomAD4 genome AF: 0.00104 AC: 158 AN: 152288 Hom.: 0 Cov.: 32 AF XY: 0.000819 AC XY: 61 AN XY: 74472

African (AFR) AF: 0.000409 AC: 17 AN: 41560

American (AMR) AF: 0.000458 AC: 7 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00187 AC: 127 AN: 68020

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00125 Hom.: 1

Bravo AF: 0.000910

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00196

EpiControl AF: 0.00160

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	7.3
DANN	Benign	0.67
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs145982146; hg19: chr7-134346745;