7-82590109-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000320415.6(MTHFD2P5):n.583G>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 0.909 in 548,800 control chromosomes in the GnomAD database, including 227,011 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 0.92 (65053 hom., cov: 32)
  • Exomes 𝑓: 0.90 (161958 hom.)
• Consequence: MTHFD2P5 ENST00000320415.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.64

Genes affected

MTHFD2P5 (HGNC:48863): (methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase pseudogene 5)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFD2P5	ENST00000320415.6	n.583G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.924 AC: 140505 AN: 152122 Hom.: 65010 Cov.: 32

Gnomad AFR AF: 0.984

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.892

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.907

Gnomad OTH AF: 0.924

GnomAD4 exome AF: 0.903 AC: 358259 AN: 396560 Hom.: 161958 Cov.: 2 AF XY: 0.904 AC XY: 201901 AN XY: 223422

Gnomad4 AFR exome AF: 0.986

Gnomad4 AMR exome AF: 0.865

Gnomad4 ASJ exome AF: 0.929

Gnomad4 EAS exome AF: 0.863

Gnomad4 SAS exome AF: 0.897

Gnomad4 FIN exome AF: 0.911

Gnomad4 NFE exome AF: 0.907

Gnomad4 OTH exome AF: 0.906

GnomAD4 genome AF: 0.924 AC: 140602 AN: 152240 Hom.: 65053 Cov.: 32 AF XY: 0.922 AC XY: 68612 AN XY: 74440

Gnomad4 AFR AF: 0.984

Gnomad4 AMR AF: 0.870

Gnomad4 ASJ AF: 0.927

Gnomad4 EAS AF: 0.866

Gnomad4 SAS AF: 0.891

Gnomad4 FIN AF: 0.916

Gnomad4 NFE AF: 0.907

Gnomad4 OTH AF: 0.918

Alfa AF: 0.911 Hom.: 83444

Bravo AF: 0.923

Asia WGS AF: 0.883 AC: 3071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	0.81
Dann	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1981576; hg19: chr7-82219425;