Variant rs1545119 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000137.4(FAH):c.553+33A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 1,610,242 control chromosomes in the GnomAD database, including 428,100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 40974 hom., cov: 29)

Exomes 𝑓: 0.73 ( 387126 hom. )

Consequence

FAH
NM_000137.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.209

Variant links:

Genes affected

FAH (HGNC:3579): (fumarylacetoacetate hydrolase) Predicted to enable fumarylacetoacetase activity. Predicted to be involved in L-phenylalanine catabolic process; homogentisate catabolic process; and tyrosine catabolic process. Predicted to act upstream of or within arginine catabolic process. Located in extracellular exosome. Implicated in tyrosinemia type I. [provided by Alliance of Genome Resources, Apr 2022]

FAH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 15-80168182-A-G is Benign according to our data. Variant chr15-80168182-A-G is described in ClinVar as [Benign]. Clinvar id is 255282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
FAH	NM_000137.4 linkuse as main transcript	c.553+33A>G	intron_variant	ENST00000561421.6	NP_000128.1
FAH	NM_001374377.1 linkuse as main transcript	c.553+33A>G	intron_variant		NP_001361306.1
FAH	NM_001374380.1 linkuse as main transcript	c.553+33A>G	intron_variant		NP_001361309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAH	ENST00000561421.6 linkuse as main transcript	c.553+33A>G		intron_variant		1	NM_000137.4	ENSP00000453347	P1	P16930-1

Frequencies

GnomAD3 genomes

AF:

0.734

AC:

111294

AN:

151576

Hom.:

40947

Cov.:

show subpopulations

Gnomad AFR

AF:

0.767

Gnomad AMI

AF:

0.774

Gnomad AMR

AF:

0.666

Gnomad ASJ

AF:

0.715

Gnomad EAS

AF:

0.876

Gnomad SAS

AF:

0.826

Gnomad FIN

AF:

0.685

Gnomad MID

AF:

0.787

Gnomad NFE

AF:

0.720

Gnomad OTH

AF:

0.751

GnomAD3 exomes

AF:

0.731

AC:

183153

AN:

250622

Hom.:

67616

AF XY:

0.738

AC XY:

100022

AN XY:

135502

show subpopulations

Gnomad AFR exome

AF:

0.767

Gnomad AMR exome

AF:

0.611

Gnomad ASJ exome

AF:

0.725

Gnomad EAS exome

AF:

0.882

Gnomad SAS exome

AF:

0.842

Gnomad FIN exome

AF:

0.683

Gnomad NFE exome

AF:

0.717

Gnomad OTH exome

AF:

0.721

GnomAD4 exome

AF:

0.727

AC:

1060366

AN:

1458552

Hom.:

387126

Cov.:

AF XY:

0.730

AC XY:

530235

AN XY:

725878

show subpopulations

Gnomad4 AFR exome

AF:

0.762

Gnomad4 AMR exome

AF:

0.618

Gnomad4 ASJ exome

AF:

0.719

Gnomad4 EAS exome

AF:

0.884

Gnomad4 SAS exome

AF:

0.841

Gnomad4 FIN exome

AF:

0.682

Gnomad4 NFE exome

AF:

0.717

Gnomad4 OTH exome

AF:

0.736

GnomAD4 genome

AF:

0.734

AC:

111373

AN:

151690

Hom.:

40974

Cov.:

AF XY:

0.734

AC XY:

54342

AN XY:

74066

show subpopulations

Gnomad4 AFR

AF:

0.767

Gnomad4 AMR

AF:

0.666

Gnomad4 ASJ

AF:

0.715

Gnomad4 EAS

AF:

0.876

Gnomad4 SAS

AF:

0.826

Gnomad4 FIN

AF:

0.685

Gnomad4 NFE

AF:

0.720

Gnomad4 OTH

AF:

0.748

Alfa

AF:

0.721

Hom.:

52591

Bravo

AF:

0.728

Asia WGS

AF:

0.815

AC:

2836

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Tyrosinemia type I

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Jul 26, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

1.6

DANN

Benign

0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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