Variant rs1370273 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.314+49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 1,598,154 control chromosomes in the GnomAD database, including 295,056 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 27935 hom., cov: 34)

Exomes 𝑓: 0.61 ( 267121 hom. )

Consequence

FAH
NM_000137.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.568

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:

FAH (HGNC:):

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=-0.88).

BP6

Variant 15-80159926-G-A is Benign according to our data. Variant chr15-80159926-G-A is described in ClinVar as [Benign]. Clinvar id is 255280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-80159926-G-A 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	Protein	UniProt
FAH	NM_000137.4 linkuse as main transcript	c.314+49G>A	intron_variant	ENST00000561421.6	NP_000128.1	P16930-1A0A384P5L6
FAH	NM_001374377.1 linkuse as main transcript	c.314+49G>A	intron_variant		NP_001361306.1
FAH	NM_001374380.1 linkuse as main transcript	c.314+49G>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.314+49G>A		intron_variant		1	NM_000137.4	ENSP00000453347.2		P16930-1

Frequencies

GnomAD3 genomes

AF:

0.604

AC:

91804

AN:

152046

Hom.:

27924

Cov.:

show subpopulations

Gnomad AFR

AF:

0.631

Gnomad AMI

AF:

0.654

Gnomad AMR

AF:

0.534

Gnomad ASJ

AF:

0.610

Gnomad EAS

AF:

0.781

Gnomad SAS

AF:

0.680

Gnomad FIN

AF:

0.505

Gnomad MID

AF:

0.677

Gnomad NFE

AF:

0.598

Gnomad OTH

AF:

0.605

GnomAD3 exomes

AF:

0.605

AC:

137742

AN:

227666

Hom.:

42013

AF XY:

0.611

AC XY:

75007

AN XY:

122700

show subpopulations

Gnomad AFR exome

AF:

0.633

Gnomad AMR exome

AF:

0.491

Gnomad ASJ exome

AF:

0.618

Gnomad EAS exome

AF:

0.786

Gnomad SAS exome

AF:

0.696

Gnomad FIN exome

AF:

0.514

Gnomad NFE exome

AF:

0.598

Gnomad OTH exome

AF:

0.582

GnomAD4 exome

AF:

0.605

AC:

875440

AN:

1445990

Hom.:

267121

Cov.:

AF XY:

0.608

AC XY:

436586

AN XY:

718118

show subpopulations

Gnomad4 AFR exome

AF:

0.629

Gnomad4 AMR exome

AF:

0.495

Gnomad4 ASJ exome

AF:

0.613

Gnomad4 EAS exome

AF:

0.798

Gnomad4 SAS exome

AF:

0.698

Gnomad4 FIN exome

AF:

0.517

Gnomad4 NFE exome

AF:

0.598

Gnomad4 OTH exome

AF:

0.614

GnomAD4 genome

AF:

0.604

AC:

91867

AN:

152164

Hom.:

27935

Cov.:

AF XY:

0.600

AC XY:

44621

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.631

Gnomad4 AMR

AF:

0.533

Gnomad4 ASJ

AF:

0.610

Gnomad4 EAS

AF:

0.781

Gnomad4 SAS

AF:

0.679

Gnomad4 FIN

AF:

0.505

Gnomad4 NFE

AF:

0.598

Gnomad4 OTH

AF:

0.602

Alfa

AF:

0.596

Hom.:

41045

Bravo

AF:

0.603

Asia WGS

AF:

0.673

AC:

2339

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Tyrosinemia type I

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.15

DANN

Benign

0.51

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