rs2385511

Variant names:

• chr1-236848497-C-A
• rs2385511
• NM_000254.3:c.1516-1847C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-236848497-C-A
• chr1-236848497-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

MTR Gene-Disease associations (from GenCC):

• methylcobalamin deficiency type cblG

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000254.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTR	NM_000254.3	MANE Select	c.1516-1847C>A		intron	N/A	NP_000245.2
	MTR	NM_001291939.1		c.1516-1847C>A		intron	N/A	NP_001278868.1
	MTR	NM_001410942.1		c.1516-1847C>A		intron	N/A	NP_001397871.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTR	ENST00000366577.10	TSL:1 MANE Select	c.1516-1847C>A		intron	N/A	ENSP00000355536.5
	MTR	ENST00000535889.6	TSL:1	c.1516-1847C>A		intron	N/A	ENSP00000441845.1
	MTR	ENST00000366576.3	TSL:1	c.178-1847C>A		intron	N/A	ENSP00000355535.3

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

African (AFR) AF: 0.831 AC: 34471 AN: 41488

American (AMR) AF: 0.670 AC: 10227 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1851 AN: 3462

East Asian (EAS) AF: 0.812 AC: 4197 AN: 5168

South Asian (SAS) AF: 0.726 AC: 3498 AN: 4820

European-Finnish (FIN) AF: 0.653 AC: 6903 AN: 10570

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.630 AC: 42845 AN: 67964

Other (OTH) AF: 0.673 AC: 1418 AN: 2108

Alfa AF: 0.654 Hom.: 11214

Bravo AF: 0.708

Asia WGS AF: 0.766 AC: 2661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.45
DANN	Benign	0.38
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2385511; hg19: chr1-237011797;