rs62078748

chr17-82097449-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004104.5(FASN):c.-8+672G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,344 control chromosomes in the GnomAD database, including 5,118 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (5114 hom., cov: 35)
  • Exomes 𝑓: 0.35 (4 hom.)
• Consequence: FASN NM_004104.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FASN	NM_004104.5	c.-8+672G>A		intron_variant		ENST00000306749.4
FASN	XM_011523538.3	c.-3+672G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FASN	ENST00000306749.4	c.-8+672G>A		intron_variant		1	NM_004104.5	P1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36402 AN: 152144 Hom.: 5115 Cov.: 35

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.0639

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.345 AC: 29 AN: 84 Hom.: 4 Cov.: 0 AF XY: 0.333 AC XY: 20 AN XY: 60

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.346

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.239 AC: 36400 AN: 152260 Hom.: 5114 Cov.: 35 AF XY: 0.238 AC XY: 17743 AN XY: 74430

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.0643

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.248

Alfa AF: 0.281 Hom.: 795

Bravo AF: 0.225

Asia WGS AF: 0.113 AC: 394 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	5.4
Dann	Benign	0.91

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: rs62078748; hg19: chr17-80055325; COSMIC: COSV60755737; COSMIC: COSV60755737;