rs1053129

Positions:

• chr5-80626901-C-A
• chr5-80626901-C-G
• chr5-80626901-C-T

Variant summary

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

The NM_000791.4(DHFR):​c.*2186G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.27 (4457 hom., cov: 18)
  • Exomes 𝑓: 0.19 (218 hom.)
  • Failed GnomAD Quality Control
• Consequence: DHFR NM_000791.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHFR	NM_000791.4	c.*2186G>T		3_prime_UTR_variant	6/6	ENST00000439211.7	NP_000782.1
DHFR	NM_001290354.2	c.*2186G>T		3_prime_UTR_variant	5/5		NP_001277283.1
DHFR	NM_001290357.2	c.*2244G>T		3_prime_UTR_variant	5/5		NP_001277286.1
DHFR	NR_110936.2	n.3067G>T		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHFR	ENST00000439211	c.*2186G>T		3_prime_UTR_variant	6/6	1	NM_000791.4	ENSP00000396308.2

Frequencies

GnomAD3 genomes AF: 0.271 AC: 33009 AN: 121596 Hom.: 4454 Cov.: 18

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.0478

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.336

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.294

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.186 AC: 3437 AN: 18488 Hom.: 218 Cov.: 0 AF XY: 0.189 AC XY: 1617 AN XY: 8556

Gnomad4 AFR exome AF: 0.231

Gnomad4 AMR exome AF: 0.151

Gnomad4 ASJ exome AF: 0.209

Gnomad4 EAS exome AF: 0.0155

Gnomad4 SAS exome AF: 0.287

Gnomad4 FIN exome AF: 0.0714

Gnomad4 NFE exome AF: 0.236

Gnomad4 OTH exome AF: 0.228

GnomAD4 genome AF: 0.271 AC: 33018 AN: 121636 Hom.: 4457 Cov.: 18 AF XY: 0.270 AC XY: 15633 AN XY: 57986

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.0480

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.292

Alfa AF: 0.0735 Hom.: 77

Bravo AF: 0.257

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.7
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1053129; hg19: chr5-79922720;