Variant 15-80152847-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001374380.1(FAH):c.-30+6G>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0092 ( 34 hom., cov: 20)

Exomes 𝑓: 0.0026 ( 14 hom. )

Consequence

FAH
NM_001374380.1 splice_donor_region, intron

Scores

Splicing: ADA: 0.00006129

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.515

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 15-80152847-G-T is Benign according to our data. Variant chr15-80152847-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1210808.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00923 (1319/142928) while in subpopulation AFR AF= 0.0295 (1104/37402). AF 95% confidence interval is 0.0281. There are 34 homozygotes in gnomad4. There are 615 alleles in male gnomad4 subpopulation. Median coverage is 20. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAH	NM_001374377.1 linkuse as main transcript	c.-88G>T		5_prime_UTR_variant	1/15		NP_001361306.1
FAH	NM_001374380.1 linkuse as main transcript	c.-30+6G>T		splice_donor_region_variant, intron_variant			NP_001361309.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	Appris	UniProt
FAH	ENST00000407106.5 linkuse as main transcript	c.-88G>T	5_prime_UTR_variant	1/15	5	ENSP00000385080	P1	P16930-1
FAH	ENST00000558767.6 linkuse as main transcript	c.-208G>T	5_prime_UTR_variant	1/5	2	ENSP00000507680
FAH	ENST00000261755.9 linkuse as main transcript	c.-30+6G>T	splice_donor_region_variant, intron_variant		5	ENSP00000261755	P1	P16930-1

Frequencies

GnomAD3 genomes

AF:

0.00921

AC:

1316

AN:

142828

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0295

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00674

Gnomad ASJ

AF:

0.0180

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000612

Gnomad OTH

AF:

0.00878

GnomAD4 exome

AF:

0.00265

AC:

1116

AN:

421750

Hom.:

Cov.:

AF XY:

0.00233

AC XY:

522

AN XY:

223608

show subpopulations

Gnomad4 AFR exome

AF:

0.0385

Gnomad4 AMR exome

AF:

0.00446

Gnomad4 ASJ exome

AF:

0.0168

Gnomad4 EAS exome

AF:

0.0000356

Gnomad4 SAS exome

AF:

0.000315

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000721

Gnomad4 OTH exome

AF:

0.00606

GnomAD4 genome

AF:

0.00923

AC:

1319

AN:

142928

Hom.:

Cov.:

AF XY:

0.00883

AC XY:

615

AN XY:

69666

show subpopulations

Gnomad4 AFR

AF:

0.0295

Gnomad4 AMR

AF:

0.00673

Gnomad4 ASJ

AF:

0.0180

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000612

Gnomad4 OTH

AF:

0.00870

Alfa

AF:

0.00957

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 06, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

6.8

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000061

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.61

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.61

Position offset: -6

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