1-236878004-A-G

Position:

• chr1-236878004-A-G

Variant summary

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

The NM_000254.3(MTR):​c.2595-2751A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 152,032 control chromosomes in the GnomAD database, including 32,323 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 0.65 (32323 hom., cov: 32)
• Consequence: MTR NM_000254.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843

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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTR	NM_000254.3	c.2595-2751A>G		intron_variant		ENST00000366577.10	NP_000245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTR	ENST00000366577.10	c.2595-2751A>G		intron_variant		1	NM_000254.3	ENSP00000355536	P1

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98662 AN: 151914 Hom.: 32289 Cov.: 32

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.650 AC: 98749 AN: 152032 Hom.: 32323 Cov.: 32 AF XY: 0.652 AC XY: 48458 AN XY: 74318

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.680

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.625

Alfa AF: 0.643 Hom.: 3917

Bravo AF: 0.654

Asia WGS AF: 0.666 AC: 2313 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.24
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: rs4659740; hg19: chr1-237041304;