chr17-17217038-C-T

Variant names:

• chr17-17217038-C-T
• rs41340844
• NM_144997.7:c.1176+31G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_144997.7(FLCN):​c.1176+31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 1,502,228 control chromosomes in the GnomAD database, including 438 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (42 hom., cov: 33)
  • Exomes 𝑓: 0.019 (396 hom.)
• Consequence: FLCN NM_144997.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.123
• Publications: 3 publications found

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:):

MPRIP (HGNC:30321): (myosin phosphatase Rho interacting protein) Enables cadherin binding activity. Predicted to be involved in actin filament organization. Located in actin cytoskeleton and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 17-17217038-C-T is Benign according to our data. Variant chr17-17217038-C-T is described in ClinVar as Benign. ClinVar VariationId is 496848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLCN	NM_144997.7	c.1176+31G>A		intron_variant	Intron 10 of 13	ENST00000285071.9	NP_659434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLCN	ENST00000285071.9	c.1176+31G>A		intron_variant	Intron 10 of 13	1	NM_144997.7	ENSP00000285071.4
ENSG00000264187	ENST00000427497.3	n.*10+31G>A		intron_variant	Intron 6 of 11	1		ENSP00000394249.3
FLCN	ENST00000577591.1	n.230G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2
MPRIP	ENST00000578209.5	c.*18-452C>T		intron_variant	Intron 5 of 5	3		ENSP00000464276.1

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2398 AN: 152158 Hom.: 42 Cov.: 33

Gnomad AFR AF: 0.00299

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0379

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0432

Gnomad FIN AF: 0.0103

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0186

Gnomad OTH AF: 0.0139

GnomAD2 exomes AF: 0.0247 AC: 6161 AN: 249196 AF XY: 0.0251

Gnomad AFR exome AF: 0.00315

Gnomad AMR exome AF: 0.0646

Gnomad ASJ exome AF: 0.0158

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0115

Gnomad NFE exome AF: 0.0178

Gnomad OTH exome AF: 0.0195

GnomAD4 exome AF: 0.0193 AC: 26112 AN: 1349952 Hom.: 396 Cov.: 20 AF XY: 0.0200 AC XY: 13555 AN XY: 677822

African (AFR) AF: 0.00247 AC: 77 AN: 31152

American (AMR) AF: 0.0623 AC: 2770 AN: 44486

Ashkenazi Jewish (ASJ) AF: 0.0157 AC: 399 AN: 25426

East Asian (EAS) AF: 0.000102 AC: 4 AN: 39176

South Asian (SAS) AF: 0.0445 AC: 3736 AN: 83900

European-Finnish (FIN) AF: 0.0105 AC: 559 AN: 53154

Middle Eastern (MID) AF: 0.0245 AC: 135 AN: 5520

European-Non Finnish (NFE) AF: 0.0174 AC: 17547 AN: 1010512

Other (OTH) AF: 0.0156 AC: 885 AN: 56626

GnomAD4 genome AF: 0.0157 AC: 2397 AN: 152276 Hom.: 42 Cov.: 33 AF XY: 0.0165 AC XY: 1231 AN XY: 74460

African (AFR) AF: 0.00298 AC: 124 AN: 41558

American (AMR) AF: 0.0379 AC: 579 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 71 AN: 3470

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5174

South Asian (SAS) AF: 0.0432 AC: 208 AN: 4816

European-Finnish (FIN) AF: 0.0103 AC: 109 AN: 10618

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0186 AC: 1262 AN: 68030

Other (OTH) AF: 0.0137 AC: 29 AN: 2110

Alfa AF: 0.0158 Hom.: 8

Bravo AF: 0.0160

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Feb 09, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.7
DANN	Benign	0.53
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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: rs41340844; hg19: chr17-17120352;