chr15-79834133-C-T

Position:

• chr15-79834133-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
LOC124903536	XR_007064730.1	n.5788G>A		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFS	ENST00000560261.1	c.*409-480G>A		intron_variant, NMD_transcript_variant		3

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

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.284

Alfa AF: 0.270 Hom.: 5661

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7166109; hg19: chr15-80126475;