Variant rs2278204 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.455+29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 1,563,212 control chromosomes in the GnomAD database, including 2,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 293 hom., cov: 33)

Exomes 𝑓: 0.018 ( 2197 hom. )

Consequence

FAH
NM_000137.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.202

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=-0.81).

BP6

Variant 15-80162365-G-A is Benign according to our data. Variant chr15-80162365-G-A is described in ClinVar as [Benign]. Clinvar id is 255281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
FAH	NM_000137.4 linkuse as main transcript	c.455+29G>A	intron_variant	ENST00000561421.6
FAH	NM_001374377.1 linkuse as main transcript	c.455+29G>A	intron_variant
FAH	NM_001374380.1 linkuse as main transcript	c.455+29G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAH	ENST00000561421.6 linkuse as main transcript	c.455+29G>A		intron_variant		1	NM_000137.4	P1	P16930-1

Frequencies

GnomAD3 genomes

AF:

0.0243

AC:

3694

AN:

152198

Hom.:

293

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00511

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0937

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.256

Gnomad SAS

AF:

0.0919

Gnomad FIN

AF:

0.00264

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00226

Gnomad OTH

AF:

0.0239

GnomAD3 exomes

AF:

0.0533

AC:

13412

AN:

251420

Hom.:

1312

AF XY:

0.0496

AC XY:

6745

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.00480

Gnomad AMR exome

AF:

0.156

Gnomad ASJ exome

AF:

0.0139

Gnomad EAS exome

AF:

0.265

Gnomad SAS exome

AF:

0.0826

Gnomad FIN exome

AF:

0.00217

Gnomad NFE exome

AF:

0.00147

Gnomad OTH exome

AF:

0.0285

GnomAD4 exome

AF:

0.0182

AC:

25651

AN:

1410896

Hom.:

2197

Cov.:

AF XY:

0.0191

AC XY:

13495

AN XY:

705038

show subpopulations

Gnomad4 AFR exome

AF:

0.00275

Gnomad4 AMR exome

AF:

0.149

Gnomad4 ASJ exome

AF:

0.0119

Gnomad4 EAS exome

AF:

0.230

Gnomad4 SAS exome

AF:

0.0774

Gnomad4 FIN exome

AF:

0.00213

Gnomad4 NFE exome

AF:

0.00104

Gnomad4 OTH exome

AF:

0.0288

GnomAD4 genome

AF:

0.0243

AC:

3700

AN:

152316

Hom.:

293

Cov.:

AF XY:

0.0275

AC XY:

2046

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00510

Gnomad4 AMR

AF:

0.0941

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.256

Gnomad4 SAS

AF:

0.0916

Gnomad4 FIN

AF:

0.00264

Gnomad4 NFE

AF:

0.00226

Gnomad4 OTH

AF:

0.0246

Alfa

AF:

0.0185

Hom.:

Bravo

AF:

0.0302

Asia WGS

AF:

0.158

AC:

550

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

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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