rs2385511

chr1-236848497-C-Achr1-236848497-C-T

Variant summary

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

The NM_000254.3(MTR):c.1516-1847C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 152,058 control chromosomes in the GnomAD database, including 37,943 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 0.70 (37943 hom., cov: 31)
• Consequence: MTR NM_000254.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.603

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTR	NM_000254.3	c.1516-1847C>A		intron_variant		ENST00000366577.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTR	ENST00000366577.10	c.1516-1847C>A		intron_variant		1	NM_000254.3	P1

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106212 AN: 151940 Hom.: 37897 Cov.: 31

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.699 AC: 106320 AN: 152058 Hom.: 37943 Cov.: 31 AF XY: 0.700 AC XY: 52068 AN XY: 74344

Gnomad4 AFR AF: 0.831

Gnomad4 AMR AF: 0.670

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.812

Gnomad4 SAS AF: 0.726

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.673

Alfa AF: 0.653 Hom.: 6648

Bravo AF: 0.708

Asia WGS AF: 0.766 AC: 2661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.45
Dann	Benign	0.38

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: rs2385511; hg19: chr1-237011797;