chr5-80654344-C-CTGGCGCGTCCCGCCCAGGT

Position:

• chr5-80654344-C-CTGGCGCGTCCCGCCCAGGT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000791.4(DHFR):​c.86+59_86+60insACCTGGGCGGGACGCGCCA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 1,562,068 control chromosomes in the GnomAD database, including 240,659 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (20790 hom., cov: 0)
  • Exomes 𝑓: 0.55 (219869 hom.)
• Consequence: DHFR NM_000791.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:2
• Conservation: PhyloP100: -0.762

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]

DHFR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 5-80654344-C-CTGGCGCGTCCCGCCCAGGT is Benign according to our data. Variant chr5-80654344-C-CTGGCGCGTCCCGCCCAGGT is described in ClinVar as [Benign]. Clinvar id is 157590.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHFR	NM_000791.4	c.86+59_86+60insACCTGGGCGGGACGCGCCA		intron_variant		ENST00000439211.7	NP_000782.1
DHFR	NM_001290354.2	c.-21+59_-21+60insACCTGGGCGGGACGCGCCA		intron_variant			NP_001277283.1
DHFR	NM_001290357.2	c.86+59_86+60insACCTGGGCGGGACGCGCCA		intron_variant			NP_001277286.1
DHFR	NR_110936.2	n.580+59_580+60insACCTGGGCGGGACGCGCCA		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHFR	ENST00000439211.7	c.86+59_86+60insACCTGGGCGGGACGCGCCA		intron_variant		1	NM_000791.4	ENSP00000396308.2

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78884 AN: 151926 Hom.: 20781 Cov.: 0

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.545

GnomAD4 exome AF: 0.555 AC: 782250 AN: 1410024 Hom.: 219869 AF XY: 0.560 AC XY: 393444 AN XY: 702570

Gnomad4 AFR exome AF: 0.440

Gnomad4 AMR exome AF: 0.413

Gnomad4 ASJ exome AF: 0.559

Gnomad4 EAS exome AF: 0.340

Gnomad4 SAS exome AF: 0.666

Gnomad4 FIN exome AF: 0.520

Gnomad4 NFE exome AF: 0.564

Gnomad4 OTH exome AF: 0.555

GnomAD4 genome AF: 0.519 AC: 78943 AN: 152044 Hom.: 20790 Cov.: 0 AF XY: 0.520 AC XY: 38654 AN XY: 74316

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.663

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.544

Alfa AF: 0.332 Hom.: 595

Asia WGS AF: 0.538 AC: 1873 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 20, 2019	This variant is associated with the following publications: (PMID: 29147684) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 18, 2021	- -

Gastrointestinal stromal tumor Uncertain:1

Uncertain significance, no assertion criteria provided

case-control

Department of Pharmacy and Biotechnology, University of Bologna

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs70991108; hg19: chr5-79950163;