rs2789352

Variant names:

• chr1-236840697-A-C
• rs2789352
• NM_000254.3:c.1515+2098A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-236840697-A-C
• chr1-236840697-A-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.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
• 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=-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 rank	MANE	Protein	UniProt
MTR	NM_000254.3	c.1515+2098A>C		intron_variant	Intron 15 of 32	ENST00000366577.10	NP_000245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTR	ENST00000366577.10	c.1515+2098A>C		intron_variant	Intron 15 of 32	1	NM_000254.3	ENSP00000355536.5
MTR	ENST00000366576.3	c.177+2179A>C		intron_variant	Intron 2 of 19	1		ENSP00000355535.3

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

African (AFR) AF: 0.916 AC: 38059 AN: 41542

American (AMR) AF: 0.680 AC: 10406 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1854 AN: 3472

East Asian (EAS) AF: 0.814 AC: 4221 AN: 5188

South Asian (SAS) AF: 0.731 AC: 3527 AN: 4826

European-Finnish (FIN) AF: 0.653 AC: 6887 AN: 10554

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.634 AC: 43108 AN: 67990

Other (OTH) AF: 0.690 AC: 1460 AN: 2116

Alfa AF: 0.638 Hom.: 23687

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
PhyloP100		-0.73
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: rs2789352; hg19: chr1-237003997;