rs3800695

Positions:

• chr7-134660791-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367

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 -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/exons	MANE	Protein	UniProt
BPGM	NM_001724.5	c.-61-656T>C		intron_variant		ENST00000344924.8	NP_001715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BPGM	ENST00000344924.8	c.-61-656T>C		intron_variant		1	NM_001724.5	ENSP00000342032.3
BPGM	ENST00000393132.2	c.-61-656T>C		intron_variant		5		ENSP00000376840.2
BPGM	ENST00000418040.5	c.-61-656T>C		intron_variant		5		ENSP00000399838.1
BPGM	ENST00000443095.1	c.-62+31T>C		intron_variant		4		ENSP00000403050.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20311 AN: 152084 Hom.: 1530 Cov.: 32

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: 41 AN: 448 Hom.: 3 Cov.: 0 AF XY: 0.0820 AC XY: 20 AN XY: 244

Gnomad4 AMR exome AF: 0.139

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0906

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.134 AC: 20342 AN: 152202 Hom.: 1535 Cov.: 32 AF XY: 0.135 AC XY: 10067 AN XY: 74394

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.0671

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.143

Alfa AF: 0.116 Hom.: 506

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
DANN	Benign	0.52

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: rs3800695; hg19: chr7-134345543;