rs60184934

Variant names:

• chr15-80153170-A-AG
• rs60184934
• NM_000137.4:c.81+38dupG

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000137.4(FAH):​c.81+38dupG 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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• tyrosinemia type I

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Laboratory for Molecular Medicine, G2P, Orphanet, Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
FAH	NM_000137.4	c.81+38dupG		intron_variant	Intron 1 of 13	ENST00000561421.6	NP_000128.1
FAH	NM_001374377.1	c.81+38dupG		intron_variant	Intron 2 of 14		NP_001361306.1
FAH	NM_001374380.1	c.81+38dupG		intron_variant	Intron 2 of 14		NP_001361309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAH	ENST00000561421.6	c.81+35_81+36insG		intron_variant	Intron 1 of 13	1	NM_000137.4	ENSP00000453347.2

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

GnomAD2 exomes AF: 0.162 AC: 37803 AN: 234040 AF XY: 0.166

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 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

African (AFR) AF: 0.246 AC: 5898 AN: 23950

American (AMR) AF: 0.0784 AC: 3396 AN: 43308

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 4201 AN: 24586

East Asian (EAS) AF: 0.291 AC: 11101 AN: 38096

South Asian (SAS) AF: 0.236 AC: 19362 AN: 81890

European-Finnish (FIN) AF: 0.176 AC: 8517 AN: 48404

Middle Eastern (MID) AF: 0.213 AC: 1143 AN: 5368

European-Non Finnish (NFE) AF: 0.115 AC: 111360 AN: 971570

Other (OTH) AF: 0.147 AC: 7891 AN: 53532

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

African (AFR) AF: 0.371 AC: 8255 AN: 22272

American (AMR) AF: 0.154 AC: 1671 AN: 10836

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 580 AN: 2998

East Asian (EAS) AF: 0.364 AC: 1213 AN: 3332

South Asian (SAS) AF: 0.299 AC: 1098 AN: 3674

European-Finnish (FIN) AF: 0.213 AC: 1737 AN: 8164

Middle Eastern (MID) AF: 0.325 AC: 89 AN: 274

European-Non Finnish (NFE) AF: 0.156 AC: 9045 AN: 58052

Other (OTH) AF: 0.215 AC: 339 AN: 1580

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

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Sep 11, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.92
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs60184934; hg19: chr15-80445512; COSMIC: COSV107237574; COSMIC: COSV107237574;