GeneBe

rs144131869

Positions:

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_000143.4(FH):​c.1237-30_1237-13del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000939 in 1,490,630 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000030 ( 0 hom., cov: 0)
Exomes 𝑓: 0.0000074 ( 0 hom. )

Consequence

FH
NM_000143.4 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.18
Variant links:
Genes affected
FH (HGNC:3700): (fumarate hydratase) The protein encoded by this gene is an enzymatic component of the tricarboxylic acid (TCA) cycle, or Krebs cycle, and catalyzes the formation of L-malate from fumarate. It exists in both a cytosolic form and an N-terminal extended form, differing only in the translation start site used. The N-terminal extended form is targeted to the mitochondrion, where the removal of the extension generates the same form as in the cytoplasm. It is similar to some thermostable class II fumarases and functions as a homotetramer. Mutations in this gene can cause fumarase deficiency and lead to progressive encephalopathy. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6
Variant 1-241500602-TGAGAGAGAGAGAGAGAGA-T is Benign according to our data. Variant chr1-241500602-TGAGAGAGAGAGAGAGAGA-T is described in Lovd as [Likely_benign].
BS2
High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FHNM_000143.4 linkuse as main transcriptc.1237-30_1237-13del splice_polypyrimidine_tract_variant, intron_variant ENST00000366560.4 NP_000134.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FHENST00000366560.4 linkuse as main transcriptc.1237-30_1237-13del splice_polypyrimidine_tract_variant, intron_variant 1 NM_000143.4 ENSP00000355518 P1P07954-1

Frequencies

GnomAD3 genomes
AF:
0.0000299
AC:
4
AN:
133802
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0000861
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000246
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000737
AC:
10
AN:
1356828
Hom.:
0
AF XY:
0.00000592
AC XY:
4
AN XY:
675472
show subpopulations
Gnomad4 AFR exome
AF:
0.0000320
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000865
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000299
AC:
4
AN:
133802
Hom.:
0
Cov.:
0
AF XY:
0.0000157
AC XY:
1
AN XY:
63768
show subpopulations
Gnomad4 AFR
AF:
0.0000861
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000246
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs144131869; hg19: chr1-241663902; API