7-117501747-CAAAAAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAA

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_000492.4(CFTR):​c.54-2482dupA 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 0.010 (14 hom., cov: 0)
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 14 AD,AR gene

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.54-2482dupA		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.54-2506_54-2505insA		intron	N/A	ENSP00000003084.6	P13569-1
	CFTR	ENST00000546407.1	TSL:1	n.167-2506_167-2505insA		intron	N/A
	CFTR	ENST00000699602.1		c.54-2506_54-2505insA		intron	N/A	ENSP00000514471.1	A0A8V8TNH2

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 447 AN: 43762 Hom.: 14 Cov.: 0

Gnomad AFR AF: 0.00653

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00776

Gnomad ASJ AF: 0.00424

Gnomad EAS AF: 0.00578

Gnomad SAS AF: 0.00862

Gnomad FIN AF: 0.00394

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0142

Gnomad OTH AF: 0.00810

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

GnomAD4 genome AF: 0.0102 AC: 447 AN: 43766 Hom.: 14 Cov.: 0 AF XY: 0.00958 AC XY: 188 AN XY: 19622

African (AFR) AF: 0.00652 AC: 97 AN: 14868

American (AMR) AF: 0.00778 AC: 25 AN: 3214

Ashkenazi Jewish (ASJ) AF: 0.00424 AC: 4 AN: 944

East Asian (EAS) AF: 0.00579 AC: 9 AN: 1554

South Asian (SAS) AF: 0.00870 AC: 9 AN: 1034

European-Finnish (FIN) AF: 0.00394 AC: 2 AN: 508

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

European-Non Finnish (NFE) AF: 0.0142 AC: 297 AN: 20926

Other (OTH) AF: 0.00803 AC: 4 AN: 498

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

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;