rs6428977

Variant names:

• chr1-236920419-A-G
• rs6428977
• XR_007066963.1:n.7189A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-236920419-A-G
• chr1-236920419-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_007066963.1(LOC105373218):​n.7189A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 152,052 control chromosomes in the GnomAD database, including 29,108 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 0.62 (29108 hom., cov: 33)
• Consequence: LOC105373218 XR_007066963.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 1 publications found

Genes affected

LOC105373218 (HGNC:):

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105373218	XR_007066963.1	n.7189A>G		non_coding_transcript_exon_variant	Exon 1 of 2
LOC105373218	XR_001738550.2	n.4239-392A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTR	ENST00000652483.1	n.895-392A>G		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93623 AN: 151934 Hom.: 29086 Cov.: 33

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.616 AC: 93698 AN: 152052 Hom.: 29108 Cov.: 33 AF XY: 0.617 AC XY: 45861 AN XY: 74312

African (AFR) AF: 0.664 AC: 27536 AN: 41462

American (AMR) AF: 0.609 AC: 9307 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1772 AN: 3470

East Asian (EAS) AF: 0.760 AC: 3916 AN: 5150

South Asian (SAS) AF: 0.633 AC: 3043 AN: 4810

European-Finnish (FIN) AF: 0.590 AC: 6243 AN: 10578

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39793 AN: 67986

Other (OTH) AF: 0.593 AC: 1253 AN: 2114

Alfa AF: 0.594 Hom.: 77405

Bravo AF: 0.621

Asia WGS AF: 0.680 AC: 2360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.43
PhyloP100		0.35

Splicing

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

Other links and lift over

dbSNP: rs6428977; hg19: chr1-237083719;