rs17139943

Variant names:

• chr7-117489437-A-G
• rs17139943
• NM_000492.4:c.53+9290A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000003084.11(CFTR):​c.53+9290A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,000 control chromosomes in the GnomAD database, including 8,647 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 0.30 (8647 hom., cov: 32)
• Consequence: CFTR ENST00000003084.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.263
• Publications: 4 publications found

Genes affected

CFTR (HGNC:1884): (CF transmembrane conductance regulator) This gene encodes a member of the ATP-binding cassette (ABC) transporter superfamily. The encoded protein functions as a chloride channel, making it unique among members of this protein family, and controls ion and water secretion and absorption in epithelial tissues. Channel activation is mediated by cycles of regulatory domain phosphorylation, ATP-binding by the nucleotide-binding domains, and ATP hydrolysis. Mutations in this gene cause cystic fibrosis, the most common lethal genetic disorder in populations of Northern European descent. The most frequently occurring mutation in cystic fibrosis, DeltaF508, results in impaired folding and trafficking of the encoded protein. Multiple pseudogenes have been identified in the human genome. [provided by RefSeq, Aug 2017]

CFTR Gene-Disease associations (from GenCC):

• cystic fibrosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Orphanet
• congenital bilateral absence of vas deferens

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary chronic pancreatitis

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000003084.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFTR	NM_000492.4	MANE Select	c.53+9290A>G		intron	N/A	NP_000483.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFTR	ENST00000003084.11	TSL:1 MANE Select	c.53+9290A>G		intron	N/A	ENSP00000003084.6
	CFTR	ENST00000546407.1	TSL:1	n.166+13629A>G		intron	N/A
	CFTR	ENST00000699602.1		c.53+9290A>G		intron	N/A	ENSP00000514471.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44877 AN: 151880 Hom.: 8637 Cov.: 32

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.263

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.296 AC: 44925 AN: 152000 Hom.: 8647 Cov.: 32 AF XY: 0.290 AC XY: 21522 AN XY: 74314

African (AFR) AF: 0.547 AC: 22691 AN: 41446

American (AMR) AF: 0.205 AC: 3118 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 413 AN: 3466

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5176

South Asian (SAS) AF: 0.115 AC: 557 AN: 4824

European-Finnish (FIN) AF: 0.258 AC: 2735 AN: 10596

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14630 AN: 67948

Other (OTH) AF: 0.260 AC: 549 AN: 2110

Alfa AF: 0.268 Hom.: 1100

Bravo AF: 0.302

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.9
DANN	Benign	0.71
PhyloP100		0.26
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: rs17139943; hg19: chr7-117129491;