rs2789352

Positions:

• chr1-236840697-A-C
• chr1-236840697-A-T

Variant summary

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

The NM_000254.3(MTR):​c.1515+2098A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,184 control chromosomes in the GnomAD database, including 41,370 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 0.73 (41370 hom., cov: 33)
• Consequence: MTR NM_000254.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.726

Genes affected

MTR (HGNC:7468): (5-methyltetrahydrofolate-homocysteine methyltransferase) This gene encodes the 5-methyltetrahydrofolate-homocysteine methyltransferase. This enzyme, also known as cobalamin-dependent methionine synthase, catalyzes the final step in methionine biosynthesis. Mutations in MTR have been identified as the underlying cause of methylcobalamin deficiency complementation group G. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTR	NM_000254.3	c.1515+2098A>C		intron_variant		ENST00000366577.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTR	ENST00000366577.10	c.1515+2098A>C		intron_variant		1	NM_000254.3	P1

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110309 AN: 152066 Hom.: 41304 Cov.: 33

Gnomad AFR AF: 0.916

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.687

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

GnomAD4 genome AF: 0.726 AC: 110440 AN: 152184 Hom.: 41370 Cov.: 33 AF XY: 0.727 AC XY: 54084 AN XY: 74396

Gnomad4 AFR AF: 0.916

Gnomad4 AMR AF: 0.680

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.814

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.634

Gnomad4 OTH AF: 0.690

Alfa AF: 0.637 Hom.: 15877

Bravo AF: 0.737

Asia WGS AF: 0.773 AC: 2684 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.64

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: rs2789352; hg19: chr1-237003997;