rs1049181

Variant names:

• chr15-80186247-A-C
• rs1049181
• NM_000137.4:c.*38A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000137.4(FAH):​c.*38A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: FAH NM_000137.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.95
• Publications: 2 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: Ambry Genetics, Myriad Women’s Health, G2P, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 15-80186247-A-C is Benign according to our data. Variant chr15-80186247-A-C is described in ClinVar as Benign. ClinVar VariationId is 255276.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000137.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAH	NM_000137.4	MANE Select	c.*38A>C		3_prime_UTR	Exon 14 of 14	NP_000128.1	A0A384P5L6
	FAH	NM_001374377.1		c.*38A>C		3_prime_UTR	Exon 15 of 15	NP_001361306.1	A0A384P5L6
	FAH	NM_001374380.1		c.*38A>C		3_prime_UTR	Exon 15 of 15	NP_001361309.1	A0A384P5L6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAH	ENST00000561421.6	TSL:1 MANE Select	c.*38A>C		3_prime_UTR	Exon 14 of 14	ENSP00000453347.2	P16930-1
	FAH	ENST00000539156.5	TSL:1	n.3326A>C		non_coding_transcript_exon	Exon 13 of 13
	FAH	ENST00000874657.1		c.*38A>C		3_prime_UTR	Exon 16 of 16	ENSP00000544716.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 17

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.41
DANN	Benign	0.56
PhyloP100		-1.9

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: rs1049181; hg19: chr15-80478589;