chr5-80629172-G-GA

Variant names:

• chr5-80629172-G-GA
• rs1747963926
• NM_000791.4:c.486-8dupT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000791.4(DHFR):​c.486-8dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: DHFR NM_000791.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHFR	NM_000791.4	c.486-8dupT		splice_region_variant, intron_variant	Intron 5 of 5	ENST00000439211.7	NP_000782.1
DHFR	NM_001290354.2	c.330-8dupT		splice_region_variant, intron_variant	Intron 4 of 4		NP_001277283.1
DHFR	NM_001290357.2	c.370-8dupT		splice_region_variant, intron_variant	Intron 4 of 4		NP_001277286.1
DHFR	NR_110936.2	n.803-8dupT		splice_region_variant, intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHFR	ENST00000439211.7	c.486-8_486-7insT		splice_region_variant, intron_variant	Intron 5 of 5	1	NM_000791.4	ENSP00000396308.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 23

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs1747963926; hg19: chr5-79924991;