chr5-80649892-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000791.4(DHFR):​c.137-398G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 679,908 control chromosomes in the GnomAD database, including 23,366 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 ( 5125 hom., cov: 32)
Exomes 𝑓: 0.25 ( 18241 hom. )

Consequence

DHFR
NM_000791.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.75
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.0).
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
DHFRNM_000791.4 linkuse as main transcriptc.137-398G>T intron_variant ENST00000439211.7
DHFRNM_001290354.2 linkuse as main transcriptc.-20-398G>T intron_variant
DHFRNM_001290357.2 linkuse as main transcriptc.137-398G>T intron_variant
DHFRNR_110936.2 linkuse as main transcriptn.581-398G>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DHFRENST00000439211.7 linkuse as main transcriptc.137-398G>T intron_variant 1 NM_000791.4 P1P00374-1

Frequencies

GnomAD3 genomes
AF:
0.254
AC:
38625
AN:
151992
Hom.:
5119
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.278
Gnomad AMI
AF:
0.254
Gnomad AMR
AF:
0.230
Gnomad ASJ
AF:
0.291
Gnomad EAS
AF:
0.0397
Gnomad SAS
AF:
0.317
Gnomad FIN
AF:
0.182
Gnomad MID
AF:
0.332
Gnomad NFE
AF:
0.265
Gnomad OTH
AF:
0.285
GnomAD4 exome
AF:
0.251
AC:
132236
AN:
527798
Hom.:
18241
AF XY:
0.255
AC XY:
71589
AN XY:
280198
show subpopulations
Gnomad4 AFR exome
AF:
0.277
Gnomad4 AMR exome
AF:
0.174
Gnomad4 ASJ exome
AF:
0.268
Gnomad4 EAS exome
AF:
0.0216
Gnomad4 SAS exome
AF:
0.329
Gnomad4 FIN exome
AF:
0.187
Gnomad4 NFE exome
AF:
0.267
Gnomad4 OTH exome
AF:
0.265
GnomAD4 genome
AF:
0.254
AC:
38652
AN:
152110
Hom.:
5125
Cov.:
32
AF XY:
0.251
AC XY:
18673
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.278
Gnomad4 AMR
AF:
0.229
Gnomad4 ASJ
AF:
0.291
Gnomad4 EAS
AF:
0.0398
Gnomad4 SAS
AF:
0.317
Gnomad4 FIN
AF:
0.182
Gnomad4 NFE
AF:
0.265
Gnomad4 OTH
AF:
0.283
Alfa
AF:
0.118
Hom.:
165
Bravo
AF:
0.255
Asia WGS
AF:
0.205
AC:
714
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.82
DANN
Benign
0.54

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs836821; hg19: chr5-79945711; API