chr15-79834133-C-T

Variant names:

• chr15-79834133-C-T
• rs7166109
• XR_007064730.1:n.5788G>A

Variant summary

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

The XR_007064730.1(LOC124903536):​n.5788G>A 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 0.309 in 151,996 control chromosomes in the GnomAD database, including 7,767 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 0.31 (7767 hom., cov: 32)
• Consequence: LOC124903536 XR_007064730.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637
• Publications: 10 publications found

Genes affected

LOC124903536 (HGNC:):

MTHFS (HGNC:7437): (methenyltetrahydrofolate synthetase) The protein encoded by this gene is an enzyme that catalyzes the conversion of 5-formyltetrahydrofolate to 5,10-methenyltetrahydrofolate, a precursor of reduced folates involved in 1-carbon metabolism. An increased activity of the encoded protein can result in an increased folate turnover rate and folate depletion. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

MTHFS Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124903536	XR_007064730.1	n.5788G>A		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFS	ENST00000560261.1	n.*409-480G>A		intron_variant	Intron 3 of 3	3		ENSP00000454318.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46918 AN: 151876 Hom.: 7744 Cov.: 32

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.309 AC: 46971 AN: 151996 Hom.: 7767 Cov.: 32 AF XY: 0.307 AC XY: 22832 AN XY: 74286

African (AFR) AF: 0.432 AC: 17893 AN: 41446

American (AMR) AF: 0.254 AC: 3890 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 874 AN: 3464

East Asian (EAS) AF: 0.241 AC: 1243 AN: 5162

South Asian (SAS) AF: 0.223 AC: 1073 AN: 4814

European-Finnish (FIN) AF: 0.274 AC: 2892 AN: 10548

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18225 AN: 67962

Other (OTH) AF: 0.284 AC: 598 AN: 2108

Alfa AF: 0.275 Hom.: 7764

Bravo AF: 0.315

Asia WGS AF: 0.230 AC: 803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.32
DANN	Benign	0.23
PhyloP100		-0.64

Splicing

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

Other links and lift over

dbSNP: rs7166109; hg19: chr15-80126475;