1-236810824-G-A

Position:

• chr1-236810824-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000254.3(MTR):​c.502+229G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,058 control chromosomes in the GnomAD database, including 8,974 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.31 (8974 hom., cov: 32)
• Consequence: MTR NM_000254.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.23

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-236810824-G-A is Benign according to our data. Variant chr1-236810824-G-A is described in ClinVar as [Benign]. Clinvar id is 1252634.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTR	NM_000254.3	c.502+229G>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.502+229G>A		intron_variant		1	NM_000254.3	ENSP00000355536	P1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47392 AN: 151940 Hom.: 8973 Cov.: 32

Gnomad AFR AF: 0.0904

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.312 AC: 47409 AN: 152058 Hom.: 8974 Cov.: 32 AF XY: 0.314 AC XY: 23351 AN XY: 74322

Gnomad4 AFR AF: 0.0903

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.323

Alfa AF: 0.362 Hom.: 2529

Bravo AF: 0.303

Asia WGS AF: 0.337 AC: 1170 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.096
DANN	Benign	0.39

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: rs4659724; hg19: chr1-236974124;