Variant rs2043691 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.961-35C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 1,536,806 control chromosomes in the GnomAD database, including 320,385 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 29395 hom., cov: 32)

Exomes 𝑓: 0.64 ( 290990 hom. )

Consequence

FAH
NM_000137.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.01

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=-0.87).

BP6

Variant 15-80180089-C-A is Benign according to our data. Variant chr15-80180089-C-A is described in ClinVar as [Benign]. Clinvar id is 255284.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
FAH	NM_000137.4 linkuse as main transcript	c.961-35C>A	intron_variant	ENST00000561421.6	NP_000128.1
FAH	NM_001374377.1 linkuse as main transcript	c.961-35C>A	intron_variant		NP_001361306.1
FAH	NM_001374380.1 linkuse as main transcript	c.961-35C>A	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.961-35C>A		intron_variant		1	NM_000137.4	ENSP00000453347	P1	P16930-1

Frequencies

GnomAD3 genomes

AF:

0.618

AC:

93868

AN:

151892

Hom.:

29378

Cov.:

show subpopulations

Gnomad AFR

AF:

0.547

Gnomad AMI

AF:

0.635

Gnomad AMR

AF:

0.576

Gnomad ASJ

AF:

0.647

Gnomad EAS

AF:

0.854

Gnomad SAS

AF:

0.729

Gnomad FIN

AF:

0.630

Gnomad MID

AF:

0.696

Gnomad NFE

AF:

0.639

Gnomad OTH

AF:

0.657

GnomAD3 exomes

AF:

0.646

AC:

154919

AN:

239904

Hom.:

50980

AF XY:

0.656

AC XY:

85580

AN XY:

130476

show subpopulations

Gnomad AFR exome

AF:

0.539

Gnomad AMR exome

AF:

0.506

Gnomad ASJ exome

AF:

0.655

Gnomad EAS exome

AF:

0.860

Gnomad SAS exome

AF:

0.755

Gnomad FIN exome

AF:

0.640

Gnomad NFE exome

AF:

0.639

Gnomad OTH exome

AF:

0.640

GnomAD4 exome

AF:

0.645

AC:

893038

AN:

1384796

Hom.:

290990

Cov.:

AF XY:

0.649

AC XY:

449597

AN XY:

692990

show subpopulations

Gnomad4 AFR exome

AF:

0.536

Gnomad4 AMR exome

AF:

0.518

Gnomad4 ASJ exome

AF:

0.650

Gnomad4 EAS exome

AF:

0.858

Gnomad4 SAS exome

AF:

0.749

Gnomad4 FIN exome

AF:

0.633

Gnomad4 NFE exome

AF:

0.637

Gnomad4 OTH exome

AF:

0.656

GnomAD4 genome

AF:

0.618

AC:

93931

AN:

152010

Hom.:

29395

Cov.:

AF XY:

0.621

AC XY:

46111

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.548

Gnomad4 AMR

AF:

0.576

Gnomad4 ASJ

AF:

0.647

Gnomad4 EAS

AF:

0.854

Gnomad4 SAS

AF:

0.729

Gnomad4 FIN

AF:

0.630

Gnomad4 NFE

AF:

0.639

Gnomad4 OTH

AF:

0.654

Alfa

AF:

0.580

Hom.:

3544

Bravo

AF:

0.605

Asia WGS

AF:

0.754

AC:

2621

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

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

-0.87

CADD

Benign

0.39

DANN

Benign

0.79

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