chr15-80152695-GCGGGGTCGGGGCAAGGGGAGGGGCGGGGCTCAGGGAGGGAGGAGAGACTGGAGGACCTGAGGCCCA-G

Position:

• chr15-80152695-GCGGGGTCGGGGCAAGGGGAGGGGCGGGGCTCAGGGAGGGAGGAGAGACTGGAGGACCTGAGGCCCA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000558022.5(FAH):​c.-30+156_-30+221del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00356 in 102,008 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (24 hom., cov: 0)
  • Exomes 𝑓: 0.0036 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAH ENST00000558022.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.12

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 15-80152695-GCGGGGTCGGGGCAAGGGGAGGGGCGGGGCTCAGGGAGGGAGGAGAGACTGGAGGACCTGAGGCCCA-G is Benign according to our data. Variant chr15-80152695-GCGGGGTCGGGGCAAGGGGAGGGGCGGGGCTCAGGGAGGGAGGAGAGACTGGAGGACCTGAGGCCCA-G is described in ClinVar as [Likely_benign]. Clinvar id is 1707388.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAH	NM_001374377.1			upstream_gene_variant			NP_001361306.1
FAH	NM_001374380.1			upstream_gene_variant			NP_001361309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAH	ENST00000558022.5	c.-30+156_-30+221del		intron_variant		4		ENSP00000453152
FAH	ENST00000261755.9			upstream_gene_variant		5		ENSP00000261755	P1
FAH	ENST00000407106.5			upstream_gene_variant		5		ENSP00000385080	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 781 AN: 74302 Hom.: 23 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00760

Gnomad ASJ AF: 0.0246

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000926

Gnomad OTH AF: 0.00918

GnomAD4 exome AF: 0.00356 AC: 363 AN: 102008 Hom.: 4 AF XY: 0.00312 AC XY: 173 AN XY: 55528

Gnomad4 AFR exome AF: 0.0806

Gnomad4 AMR exome AF: 0.00992

Gnomad4 ASJ exome AF: 0.0323

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000482

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00105

Gnomad4 OTH exome AF: 0.00698

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0105 AC: 781 AN: 74324 Hom.: 24 Cov.: 0 AF XY: 0.0102 AC XY: 367 AN XY: 35876

Gnomad4 AFR AF: 0.0369

Gnomad4 AMR AF: 0.00758

Gnomad4 ASJ AF: 0.0246

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000926

Gnomad4 OTH AF: 0.00913

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 25, 2019

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-80445037;