7-117501747-CAAAAAAAAAAAAAAAA-CAAAAAAAAAAAAAAA

Variant names:

• chr7-117501747-CA-C
• rs1212853305
• NM_000492.4:c.54-2482delA

Variant summary

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

The NM_000492.4(CFTR):​c.54-2482delA 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 0.22 (142 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.54-2482delA		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.54-2505delA		intron	N/A	ENSP00000003084.6	P13569-1
	CFTR	ENST00000546407.1	TSL:1	n.167-2505delA		intron	N/A
	CFTR	ENST00000699602.1		c.54-2505delA		intron	N/A	ENSP00000514471.1	A0A8V8TNH2

Frequencies

GnomAD3 genomes AF: 0.220 AC: 9665 AN: 43944 Hom.: 144 Cov.: 0

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.00514

Gnomad SAS AF: 0.0740

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.333

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.235

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: 0.220 AC: 9668 AN: 43948 Hom.: 142 Cov.: 0 AF XY: 0.219 AC XY: 4325 AN XY: 19724

African (AFR) AF: 0.323 AC: 4813 AN: 14920

American (AMR) AF: 0.150 AC: 484 AN: 3228

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 217 AN: 950

East Asian (EAS) AF: 0.00515 AC: 8 AN: 1554

South Asian (SAS) AF: 0.0718 AC: 75 AN: 1044

European-Finnish (FIN) AF: 0.146 AC: 74 AN: 508

Middle Eastern (MID) AF: 0.333 AC: 10 AN: 30

European-Non Finnish (NFE) AF: 0.182 AC: 3836 AN: 21030

Other (OTH) AF: 0.233 AC: 115 AN: 494

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;