7-117597830-CG-CGG

Variant names:

• chr7-117597830-C-CG
• rs958360753
• NM_000492.4:c.2619+2779dupG

Variant summary

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

The NM_000492.4(CFTR):​c.2619+2779dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 149,668 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0012 (0 hom., cov: 32)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125
• 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.2619+2779dupG		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.2619+2772_2619+2773insG		intron	N/A	ENSP00000003084.6	P13569-1
	CFTR	ENST00000699602.1		c.2619+2772_2619+2773insG		intron	N/A	ENSP00000514471.1	A0A8V8TNH2
	CFTR	ENST00000889206.1		c.2532+2772_2532+2773insG		intron	N/A	ENSP00000559265.1

Frequencies

GnomAD3 genomes AF: 0.00116 AC: 174 AN: 149602 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000885

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000466

Gnomad ASJ AF: 0.00780

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.000844

Gnomad FIN AF: 0.000205

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00139

Gnomad OTH AF: 0.000975

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

GnomAD4 genome AF: 0.00119 AC: 178 AN: 149668 Hom.: 0 Cov.: 32 AF XY: 0.00111 AC XY: 81 AN XY: 73002

African (AFR) AF: 0.000981 AC: 40 AN: 40758

American (AMR) AF: 0.000466 AC: 7 AN: 15030

Ashkenazi Jewish (ASJ) AF: 0.00780 AC: 27 AN: 3460

East Asian (EAS) AF: 0.000389 AC: 2 AN: 5140

South Asian (SAS) AF: 0.000846 AC: 4 AN: 4728

European-Finnish (FIN) AF: 0.000205 AC: 2 AN: 9764

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.00139 AC: 94 AN: 67530

Other (OTH) AF: 0.000967 AC: 2 AN: 2068

Alfa AF: 0.000216 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.13

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: rs958360753; hg19: chr7-117237884; COSMIC: COSV50084550;