rs60184934

Positions:

• chr15-80153170-A-AG
• chr15-80153170-A-AGGGGAG
• chr15-80153170-A-AGGGGAGTGGAGTGGAGTGGAG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000137.4(FAH):​c.81+38dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (2236 hom., cov: 20)
  • Exomes 𝑓: 0.13 (15195 hom.)
• Consequence: FAH NM_000137.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.921

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 -16 ACMG points.

• BP6: Variant 15-80153170-A-AG is Benign according to our data. Variant chr15-80153170-A-AG is described in ClinVar as [Benign]. Clinvar id is 255283.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAH	NM_000137.4	c.81+38dup		intron_variant		ENST00000561421.6
FAH	NM_001374377.1	c.81+38dup		intron_variant
FAH	NM_001374380.1	c.81+38dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAH	ENST00000561421.6	c.81+38dup		intron_variant		1	NM_000137.4	P1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 24126 AN: 111846 Hom.: 2236 Cov.: 20

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.212

GnomAD3 exomes AF: 0.162 AC: 37803 AN: 234040 Hom.: 3381 AF XY: 0.166 AC XY: 21265 AN XY: 128198

Gnomad AFR exome AF: 0.258

Gnomad AMR exome AF: 0.0765

Gnomad ASJ exome AF: 0.173

Gnomad EAS exome AF: 0.280

Gnomad SAS exome AF: 0.242

Gnomad FIN exome AF: 0.178

Gnomad NFE exome AF: 0.133

Gnomad OTH exome AF: 0.154

GnomAD4 exome AF: 0.134 AC: 172869 AN: 1290704 Hom.: 15195 Cov.: 20 AF XY: 0.139 AC XY: 89971 AN XY: 649306

Gnomad4 AFR exome AF: 0.246

Gnomad4 AMR exome AF: 0.0784

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.291

Gnomad4 SAS exome AF: 0.236

Gnomad4 FIN exome AF: 0.176

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.216 AC: 24154 AN: 111914 Hom.: 2236 Cov.: 20 AF XY: 0.221 AC XY: 12011 AN XY: 54288

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.215

Alfa AF: 0.0952 Hom.: 165

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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

clinical testing

GeneDx

Sep 11, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs60184934; hg19: chr15-80445512;