Variant chr5-80633921-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000791.4(DHFR):c.441G>A(p.Thr147Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000763 in 1,612,738 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00080 ( 2 hom. )

Consequence

DHFR
NM_000791.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.12

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]

DHFR links:

DHFR (HGNC:):

DHFR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 5-80633921-C-T is Benign according to our data. Variant chr5-80633921-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 723950.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.12 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHFR	NM_000791.4 linkuse as main transcript	c.441G>A	p.Thr147Thr	synonymous_variant	5/6	ENST00000439211.7	NP_000782.1	P00374-1B0YJ76
DHFR	NM_001290354.2 linkuse as main transcript	c.285G>A	p.Thr95Thr	synonymous_variant	4/5		NP_001277283.1	P00374-2
DHFR	NM_001290357.2 linkuse as main transcript	c.369+3962G>A		intron_variant			NP_001277286.1	B4DM58
DHFR	NR_110936.2 linkuse as main transcript	n.758G>A		non_coding_transcript_exon_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHFR	ENST00000439211.7 linkuse as main transcript	c.441G>A	p.Thr147Thr	synonymous_variant	5/6	1	NM_000791.4	ENSP00000396308.2		P00374-1

Frequencies

GnomAD3 genomes

AF:

0.000434

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000656

AC:

164

AN:

249976

Hom.:

AF XY:

0.000701

AC XY:

AN XY:

135584

show subpopulations

Gnomad AFR exome

AF:

0.000258

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.000647

Gnomad NFE exome

AF:

0.000848

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.000797

AC:

1164

AN:

1460526

Hom.:

Cov.:

AF XY:

0.000787

AC XY:

572

AN XY:

726582

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00101

Gnomad4 FIN exome

AF:

0.000880

Gnomad4 NFE exome

AF:

0.000846

Gnomad4 OTH exome

AF:

0.00114

GnomAD4 genome

AF:

0.000434

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000378

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000625

Hom.:

Bravo

AF:

0.000461

EpiCase

AF:

0.000601

EpiControl

AF:

0.000948

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 08, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.1

DANN

Benign

0.61

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over