7-117493359-G-GA

Variant names:

• chr7-117493359-G-GA
• rs556683713
• NM_000492.4:c.54-10886dupA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000492.4(CFTR):​c.54-10886dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 151,830 control chromosomes in the GnomAD database, including 23 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.011 (23 hom., cov: 32)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204
• 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0107 (1618/151830) while in subpopulation AFR AF = 0.0365 (1513/41442). AF 95% confidence interval is 0.035. There are 23 homozygotes in GnomAd4. There are 761 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 23 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.54-10886dupA		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.54-10894_54-10893insA		intron	N/A	ENSP00000003084.6	P13569-1
	CFTR	ENST00000546407.1	TSL:1	n.167-10894_167-10893insA		intron	N/A
	CFTR	ENST00000699602.1		c.54-10894_54-10893insA		intron	N/A	ENSP00000514471.1	A0A8V8TNH2

Frequencies

GnomAD3 genomes AF: 0.0107 AC: 1619 AN: 151712 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.0366

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00381

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.0000949

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000442

Gnomad OTH AF: 0.00721

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

GnomAD4 genome AF: 0.0107 AC: 1618 AN: 151830 Hom.: 23 Cov.: 32 AF XY: 0.0103 AC XY: 761 AN XY: 74228

African (AFR) AF: 0.0365 AC: 1513 AN: 41442

American (AMR) AF: 0.00381 AC: 58 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.0000949 AC: 1 AN: 10532

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000427 AC: 29 AN: 67884

Other (OTH) AF: 0.00714 AC: 15 AN: 2102

Alfa AF: 0.0000547 Hom.: 0

Bravo AF: 0.0123

Asia WGS AF: 0.00375 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.20
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: rs556683713; hg19: chr7-117133413;