rs7387

Positions:

• chr5-80628972-T-A

Variant summary

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

The NM_000791.4(DHFR):​c.*115A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 585,468 control chromosomes in the GnomAD database, including 19,691 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 0.25 (5120 hom., cov: 30)
  • Exomes 𝑓: 0.25 (14571 hom.)
• Consequence: DHFR NM_000791.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DHFR	NM_000791.4	c.*115A>T		3_prime_UTR_variant	6/6	ENST00000439211.7
DHFR	NM_001290354.2	c.*115A>T		3_prime_UTR_variant	5/5
DHFR	NM_001290357.2	c.*173A>T		3_prime_UTR_variant	5/5
DHFR	NR_110936.2	n.996A>T		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHFR	ENST00000439211.7	c.*115A>T		3_prime_UTR_variant	6/6	1	NM_000791.4	P1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38560 AN: 151784 Hom.: 5114 Cov.: 30

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.0399

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.284

GnomAD4 exome AF: 0.246 AC: 106652 AN: 433566 Hom.: 14571 Cov.: 5 AF XY: 0.251 AC XY: 57407 AN XY: 229116

Gnomad4 AFR exome AF: 0.279

Gnomad4 AMR exome AF: 0.187

Gnomad4 ASJ exome AF: 0.269

Gnomad4 EAS exome AF: 0.0214

Gnomad4 SAS exome AF: 0.327

Gnomad4 FIN exome AF: 0.183

Gnomad4 NFE exome AF: 0.267

Gnomad4 OTH exome AF: 0.263

GnomAD4 genome AF: 0.254 AC: 38587 AN: 151902 Hom.: 5120 Cov.: 30 AF XY: 0.251 AC XY: 18636 AN XY: 74256

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.0400

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.282

Alfa AF: 0.253 Hom.: 580

Bravo AF: 0.255

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	9.4
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7387; hg19: chr5-79924791;