rs376210775

Variant names:

• chr7-134661843-G-A
• rs376210775
• NM_001724.5:c.336G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-134661843-G-A
• chr7-134661843-G-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_001724.5(BPGM):​c.336G>A​(p.Val112Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,608,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: BPGM NM_001724.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.86
• 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics

LOC124901750 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 7-134661843-G-A is Benign according to our data. Variant chr7-134661843-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3715256.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.86 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.336G>A	p.Val112Val	synonymous	Exon 2 of 3	NP_001715.1	P07738
	BPGM	NM_001293085.2		c.336G>A	p.Val112Val	synonymous	Exon 3 of 4	NP_001280014.1	P07738
	BPGM	NM_199186.3		c.336G>A	p.Val112Val	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.336G>A	p.Val112Val	synonymous	Exon 2 of 3	ENSP00000342032.3	P07738
	BPGM	ENST00000393132.2	TSL:5	c.336G>A	p.Val112Val	synonymous	Exon 3 of 4	ENSP00000376840.2	P07738
	BPGM	ENST00000418040.5	TSL:5	c.336G>A	p.Val112Val	synonymous	Exon 3 of 4	ENSP00000399838.1	P07738

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 247662 AF XY: 0.00

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000481 AC: 7 AN: 1455948 Hom.: 0 Cov.: 31 AF XY: 0.00000415 AC XY: 3 AN XY: 723576

African (AFR) AF: 0.0000904 AC: 3 AN: 33192

American (AMR) AF: 0.0000226 AC: 1 AN: 44216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25760

East Asian (EAS) AF: 0.00 AC: 0 AN: 39610

South Asian (SAS) AF: 0.00 AC: 0 AN: 85706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1108438

Other (OTH) AF: 0.0000167 AC: 1 AN: 60040

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152282 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74460

African (AFR) AF: 0.000385 AC: 16 AN: 41552

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000203 Hom.: 0

Bravo AF: 0.0000907

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	10
DANN	Benign	0.72
PhyloP100		2.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs376210775; hg19: chr7-134346595;