7-117501747-CAAAAAAAAAAAAAAAA-CAAAAAAAAAAAAAA

Variant names:

• chr7-117501747-CAA-C
• rs1212853305
• NM_000492.4:c.54-2483_54-2482delAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000492.4(CFTR):​c.54-2483_54-2482delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (47 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.685
• Publications: 0 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: Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Laboratory for Molecular Medicine
• 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000492.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFTR	NM_000492.4	MANE Select	c.54-2483_54-2482delAA		intron	N/A	NP_000483.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFTR	ENST00000003084.11	TSL:1 MANE Select	c.54-2505_54-2504delAA		intron	N/A	ENSP00000003084.6	P13569-1
	CFTR	ENST00000546407.1	TSL:1	n.167-2505_167-2504delAA		intron	N/A
	CFTR	ENST00000699602.1		c.54-2505_54-2504delAA		intron	N/A	ENSP00000514471.1	A0A8V8TNH2

Frequencies

GnomAD3 genomes AF: 0.136 AC: 5855 AN: 43172 Hom.: 49 Cov.: 0

Gnomad AFR AF: 0.0714

Gnomad AMI AF: 0.0753

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.0843

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.133

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.136 AC: 5852 AN: 43176 Hom.: 47 Cov.: 0 AF XY: 0.138 AC XY: 2677 AN XY: 19346

African (AFR) AF: 0.0717 AC: 1065 AN: 14854

American (AMR) AF: 0.255 AC: 799 AN: 3128

Ashkenazi Jewish (ASJ) AF: 0.0798 AC: 75 AN: 940

East Asian (EAS) AF: 0.430 AC: 628 AN: 1462

South Asian (SAS) AF: 0.342 AC: 339 AN: 992

European-Finnish (FIN) AF: 0.0843 AC: 43 AN: 510

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 30

European-Non Finnish (NFE) AF: 0.137 AC: 2825 AN: 20588

Other (OTH) AF: 0.132 AC: 64 AN: 486

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.69
Mutation Taster		=100/0	polymorphism

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: rs1212853305; hg19: chr7-117141801;