Variant 17-82082170-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004104.5(FASN):c.6012-10G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00427 in 1,601,698 control chromosomes in the GnomAD database, including 262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 143 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 119 hom. )

Consequence

FASN
NM_004104.5 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0005676

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.63

Variant links:

Genes affected

FASN (HGNC:3594): (fatty acid synthase) The enzyme encoded by this gene is a multifunctional protein. Its main function is to catalyze the synthesis of palmitate from acetyl-CoA and malonyl-CoA, in the presence of NADPH, into long-chain saturated fatty acids. In some cancer cell lines, this protein has been found to be fused with estrogen receptor-alpha (ER-alpha), in which the N-terminus of FAS is fused in-frame with the C-terminus of ER-alpha. [provided by RefSeq, Jul 2008]

FASN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 17-82082170-C-T is Benign according to our data. Variant chr17-82082170-C-T is described in ClinVar as [Benign]. Clinvar id is 462087.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FASN	NM_004104.5 linkuse as main transcript	c.6012-10G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000306749.4
FASN	XM_011523538.3 linkuse as main transcript	c.6012-10G>A		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FASN	ENST00000306749.4 linkuse as main transcript	c.6012-10G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004104.5	P1
FASN	ENST00000634990.1 linkuse as main transcript	c.6006-10G>A		splice_polypyrimidine_tract_variant, intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0233

AC:

3549

AN:

152156

Hom.:

143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0813

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00884

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00607

AC:

1462

AN:

240714

Hom.:

AF XY:

0.00452

AC XY:

594

AN XY:

131304

show subpopulations

Gnomad AFR exome

AF:

0.0824

Gnomad AMR exome

AF:

0.00299

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000658

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000983

Gnomad OTH exome

AF:

0.00199

GnomAD4 exome

AF:

0.00227

AC:

3284

AN:

1449426

Hom.:

119

Cov.:

AF XY:

0.00194

AC XY:

1403

AN XY:

721362

show subpopulations

Gnomad4 AFR exome

AF:

0.0805

Gnomad4 AMR exome

AF:

0.00380

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000983

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000675

Gnomad4 OTH exome

AF:

0.00451

GnomAD4 genome

AF:

0.0234

AC:

3556

AN:

152272

Hom.:

143

Cov.:

AF XY:

0.0223

AC XY:

1658

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0812

Gnomad4 AMR

AF:

0.00883

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0127

Hom.:

Bravo

AF:

0.0262

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

FASN-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Epileptic encephalopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.064

DANN

Benign

0.66

RBP_binding_hub_radar

0.67

RBP_regulation_power_radar

1.8

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00057

dbscSNV1_RF

Benign

0.010

SpliceAI score (max)

0.020

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

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