rs2359720

chr2-206743785-T-Achr2-206743785-T-Cchr2-206743785-T-G

Variant summary

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

The NM_001039845.3(MDH1B):c.1408+1837A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 151,894 control chromosomes in the GnomAD database, including 8,539 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 0.29 (8539 hom., cov: 31)
• Consequence: MDH1B NM_001039845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75

Genes affected

MDH1B (HGNC:17836): (malate dehydrogenase 1B) Predicted to enable L-malate dehydrogenase activity. Predicted to be involved in NADH metabolic process; dicarboxylic acid metabolic process; and tricarboxylic acid cycle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MDH1B	NM_001039845.3	c.1408+1837A>T		intron_variant		ENST00000374412.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDH1B	ENST00000374412.8	c.1408+1837A>T		intron_variant		1	NM_001039845.3	P4

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43584 AN: 151776 Hom.: 8511 Cov.: 31

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.267

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.287 AC: 43651 AN: 151894 Hom.: 8539 Cov.: 31 AF XY: 0.293 AC XY: 21770 AN XY: 74244

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.566

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.267

Alfa AF: 0.0714 Hom.: 80

Bravo AF: 0.318

Asia WGS AF: 0.456 AC: 1587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	12
Dann	Benign	0.89

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: rs2359720; hg19: chr2-207608509;