rs41337846

Variant names:

• chr17-17235918-T-C
• rs41337846
• NM_144997.7:c.-228+994A>G

Variant summary

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

The NM_144997.7(FLCN):​c.-228+994A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,108 control chromosomes in the GnomAD database, including 1,949 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 0.15 (1947 hom., cov: 32)
  • Exomes 𝑓: 0.17 (2 hom.)
• Consequence: FLCN NM_144997.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.92

Genes affected

FLCN (HGNC:27310): (folliculin) This gene is located within the Smith-Magenis syndrome region on chromosome 17. Mutations in this gene are associated with Birt-Hogg-Dube syndrome, which is characterized by fibrofolliculomas, renal tumors, lung cysts, and pneumothorax. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ENSG00000264187 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLCN	NM_144997.7	c.-228+994A>G		intron_variant	Intron 1 of 13	ENST00000285071.9	NP_659434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLCN	ENST00000285071.9	c.-228+994A>G		intron_variant	Intron 1 of 13	1	NM_144997.7	ENSP00000285071.4
ENSG00000264187	ENST00000427497.3	n.-228+994A>G		intron_variant	Intron 1 of 11	1		ENSP00000394249.3

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22500 AN: 151960 Hom.: 1944 Cov.: 32

Gnomad AFR AF: 0.0561

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.172

GnomAD4 exome AF: 0.167 AC: 5 AN: 30 Hom.: 2 Cov.: 0 AF XY: 0.250 AC XY: 5 AN XY: 20

Gnomad4 NFE exome AF: 0.192

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.148 AC: 22516 AN: 152078 Hom.: 1947 Cov.: 32 AF XY: 0.149 AC XY: 11083 AN XY: 74336

Gnomad4 AFR AF: 0.0562

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.174

Alfa AF: 0.155 Hom.: 283

Bravo AF: 0.146

Asia WGS AF: 0.189 AC: 660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.48

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: rs41337846; hg19: chr17-17139232;