chr1-236869508-G-A

Position:

• chr1-236869508-G-A

Variant summary

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

The NM_000254.3(MTR):​c.2406-4265G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0783 in 152,180 control chromosomes in the GnomAD database, including 944 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 0.078 (944 hom., cov: 33)
• Consequence: MTR NM_000254.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.868

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTR	NM_000254.3	c.2406-4265G>A		intron_variant		ENST00000366577.10	NP_000245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTR	ENST00000366577.10	c.2406-4265G>A		intron_variant		1	NM_000254.3	ENSP00000355536	P1

Frequencies

GnomAD3 genomes AF: 0.0782 AC: 11887 AN: 152062 Hom.: 939 Cov.: 33

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0640

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.0683

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0354

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0162

Gnomad OTH AF: 0.0612

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

GnomAD4 genome AF: 0.0783 AC: 11923 AN: 152180 Hom.: 944 Cov.: 33 AF XY: 0.0799 AC XY: 5944 AN XY: 74382

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.0643

Gnomad4 ASJ AF: 0.0291

Gnomad4 EAS AF: 0.0679

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.0354

Gnomad4 NFE AF: 0.0163

Gnomad4 OTH AF: 0.0653

Alfa AF: 0.0527 Hom.: 71

Bravo AF: 0.0847

Asia WGS AF: 0.104 AC: 359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
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: rs10495386; hg19: chr1-237032808;