5-80626211-C-T

Position:

• chr5-80626211-C-T

Variant summary

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

The 5-80626211-C-T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 201,964 control chromosomes in the GnomAD database, including 1,702 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 0.12 (1219 hom., cov: 29)
  • Exomes 𝑓: 0.12 (483 hom.)
• Consequence: DHFR NM_000791.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.770

Genes affected

DHFR (HGNC:2861): (dihydrofolate reductase) Dihydrofolate reductase converts dihydrofolate into tetrahydrofolate, a methyl group shuttle required for the de novo synthesis of purines, thymidylic acid, and certain amino acids. While the functional dihydrofolate reductase gene has been mapped to chromosome 5, multiple intronless processed pseudogenes or dihydrofolate reductase-like genes have been identified on separate chromosomes. Dihydrofolate reductase deficiency has been linked to megaloblastic anemia. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHFR	NM_000791.4			downstream_gene_variant		ENST00000439211.7	NP_000782.1
DHFR	NM_001290354.2			downstream_gene_variant			NP_001277283.1
DHFR	NM_001290357.2			downstream_gene_variant			NP_001277286.1
DHFR	NR_110936.2			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHFR	ENST00000439211.7			downstream_gene_variant		1	NM_000791.4	ENSP00000396308	P1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18029 AN: 152042 Hom.: 1219 Cov.: 29

Gnomad AFR AF: 0.0583

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.124 AC: 6190 AN: 49804 Hom.: 483 Cov.: 0 AF XY: 0.126 AC XY: 2918 AN XY: 23102

Gnomad4 AFR exome AF: 0.0561

Gnomad4 AMR exome AF: 0.101

Gnomad4 ASJ exome AF: 0.160

Gnomad4 EAS exome AF: 0.000123

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.0556

Gnomad4 NFE exome AF: 0.157

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.118 AC: 18024 AN: 152160 Hom.: 1219 Cov.: 29 AF XY: 0.117 AC XY: 8680 AN XY: 74388

Gnomad4 AFR AF: 0.0583

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.139

Alfa AF: 0.157 Hom.: 2110

Bravo AF: 0.117

Asia WGS AF: 0.0710 AC: 249 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.49
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1650723; hg19: chr5-79922030;