7-82590109-C-T

Variant names:

• chr7-82590109-C-T
• rs1981576
• ENST00000320415.6:n.583G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MTHFD2P5		n.82590109C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFD2P5	ENST00000320415.6	n.583G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

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

African (AFR) AF: 0.986 AC: 11040 AN: 11198

American (AMR) AF: 0.865 AC: 30562 AN: 35338

Ashkenazi Jewish (ASJ) AF: 0.929 AC: 10865 AN: 11692

East Asian (EAS) AF: 0.863 AC: 13938 AN: 16142

South Asian (SAS) AF: 0.897 AC: 57179 AN: 63750

European-Finnish (FIN) AF: 0.911 AC: 29055 AN: 31898

Middle Eastern (MID) AF: 0.950 AC: 1237 AN: 1302

European-Non Finnish (NFE) AF: 0.907 AC: 187657 AN: 206786

Other (OTH) AF: 0.906 AC: 16726 AN: 18454

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

African (AFR) AF: 0.984 AC: 40878 AN: 41550

American (AMR) AF: 0.870 AC: 13302 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.927 AC: 3220 AN: 3472

East Asian (EAS) AF: 0.866 AC: 4475 AN: 5168

South Asian (SAS) AF: 0.891 AC: 4301 AN: 4828

European-Finnish (FIN) AF: 0.916 AC: 9704 AN: 10594

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.907 AC: 61679 AN: 68024

Other (OTH) AF: 0.918 AC: 1937 AN: 2110

Alfa AF: 0.917 Hom.: 122502

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
PhyloP100		-2.6

Splicing

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

Other links and lift over

dbSNP: rs1981576; hg19: chr7-82219425;