Variant 15-80159733-T-C 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.193-23T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 1,613,044 control chromosomes in the GnomAD database, including 296,782 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 27377 hom., cov: 32)

Exomes 𝑓: 0.60 ( 269405 hom. )

Consequence

FAH
NM_000137.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.137

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 15-80159733-T-C is Benign according to our data. Variant chr15-80159733-T-C is described in ClinVar as [Benign]. Clinvar id is 255279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-80159733-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
FAH	NM_000137.4 linkuse as main transcript	c.193-23T>C	intron_variant	ENST00000561421.6
FAH	NM_001374377.1 linkuse as main transcript	c.193-23T>C	intron_variant
FAH	NM_001374380.1 linkuse as main transcript	c.193-23T>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAH	ENST00000561421.6 linkuse as main transcript	c.193-23T>C		intron_variant		1	NM_000137.4	P1	P16930-1

Frequencies

GnomAD3 genomes

AF:

0.598

AC:

90895

AN:

151952

Hom.:

27368

Cov.:

show subpopulations

Gnomad AFR

AF:

0.611

Gnomad AMI

AF:

0.654

Gnomad AMR

AF:

0.533

Gnomad ASJ

AF:

0.610

Gnomad EAS

AF:

0.781

Gnomad SAS

AF:

0.680

Gnomad FIN

AF:

0.504

Gnomad MID

AF:

0.677

Gnomad NFE

AF:

0.599

Gnomad OTH

AF:

0.600

GnomAD3 exomes

AF:

0.602

AC:

151352

AN:

251466

Hom.:

46456

AF XY:

0.608

AC XY:

82672

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.612

Gnomad AMR exome

AF:

0.488

Gnomad ASJ exome

AF:

0.617

Gnomad EAS exome

AF:

0.785

Gnomad SAS exome

AF:

0.695

Gnomad FIN exome

AF:

0.513

Gnomad NFE exome

AF:

0.597

Gnomad OTH exome

AF:

0.580

GnomAD4 exome

AF:

0.605

AC:

883318

AN:

1460974

Hom.:

269405

Cov.:

AF XY:

0.607

AC XY:

441432

AN XY:

726852

show subpopulations

Gnomad4 AFR exome

AF:

0.608

Gnomad4 AMR exome

AF:

0.492

Gnomad4 ASJ exome

AF:

0.613

Gnomad4 EAS exome

AF:

0.799

Gnomad4 SAS exome

AF:

0.698

Gnomad4 FIN exome

AF:

0.517

Gnomad4 NFE exome

AF:

0.598

Gnomad4 OTH exome

AF:

0.612

GnomAD4 genome

AF:

0.598

AC:

90953

AN:

152070

Hom.:

27377

Cov.:

AF XY:

0.594

AC XY:

44198

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.611

Gnomad4 AMR

AF:

0.532

Gnomad4 ASJ

AF:

0.610

Gnomad4 EAS

AF:

0.782

Gnomad4 SAS

AF:

0.679

Gnomad4 FIN

AF:

0.504

Gnomad4 NFE

AF:

0.599

Gnomad4 OTH

AF:

0.598

Alfa

AF:

0.604

Hom.:

14379

Bravo

AF:

0.596

Asia WGS

AF:

0.670

AC:

2331

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

7.0

DANN

Benign

0.81

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