rs11806016

Variant names:

• chr1-236906015-C-T
• rs11806016
• ENST00000650888.1:n.*4306-1030C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000650888.1(MTR):​n.*4306-1030C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0249 in 152,064 control chromosomes in the GnomAD database, including 85 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 0.025 (85 hom., cov: 32)
• Consequence: MTR ENST00000650888.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410
• Publications: 2 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=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0249 (3788/152064) while in subpopulation NFE AF = 0.0413 (2809/67966). AF 95% confidence interval is 0.0401. There are 85 homozygotes in GnomAd4. There are 1690 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 85 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTR	ENST00000650888.1	n.*4306-1030C>T		intron_variant	Intron 31 of 32			ENSP00000498393.1
MTR	ENST00000652483.1	n.587+6906C>T		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3788 AN: 151946 Hom.: 85 Cov.: 32

Gnomad AFR AF: 0.00723

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.0202

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00958

Gnomad FIN AF: 0.0101

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0413

Gnomad OTH AF: 0.0203

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

GnomAD4 genome AF: 0.0249 AC: 3788 AN: 152064 Hom.: 85 Cov.: 32 AF XY: 0.0227 AC XY: 1690 AN XY: 74328

African (AFR) AF: 0.00720 AC: 299 AN: 41500

American (AMR) AF: 0.0202 AC: 309 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00959 AC: 46 AN: 4798

European-Finnish (FIN) AF: 0.0101 AC: 107 AN: 10578

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0413 AC: 2809 AN: 67966

Other (OTH) AF: 0.0200 AC: 42 AN: 2096

Alfa AF: 0.0372 Hom.: 92

Bravo AF: 0.0259

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.9
DANN	Benign	0.34
PhyloP100		0.041

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11806016; hg19: chr1-237069315;