7-134661993-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001724.5(BPGM):c.486G>A(p.Leu162=) 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, single submitter B:1
• Conservation: PhyloP100: 1.15

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]

LOC124901750 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -7 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 id is 2759959.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.15 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BPGM	NM_001724.5	c.486G>A	p.Leu162=	synonymous_variant	2/3	ENST00000344924.8
LOC124901750	XR_007060537.1	n.29222-42045C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BPGM	ENST00000344924.8	c.486G>A	p.Leu162=	synonymous_variant	2/3	1	NM_001724.5	P1
BPGM	ENST00000393132.2	c.486G>A	p.Leu162=	synonymous_variant	3/4	5		P1
BPGM	ENST00000418040.5	c.486G>A	p.Leu162=	synonymous_variant	3/4	5		P1

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

GnomAD3 exomes AF: 0.000907 AC: 228 AN: 251374 Hom.: 0 AF XY: 0.000876 AC XY: 119 AN XY: 135842

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 SAS exome AF: 0.000359

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

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.0000895

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000267

Gnomad4 FIN exome AF: 0.000262

Gnomad4 NFE exome AF: 0.00221

Gnomad4 OTH exome AF: 0.00127

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

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00187

Gnomad4 OTH AF: 0.000947

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

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Sep 27, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	7.3
Dann	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs145982146; hg19: chr7-134346745;