7-117504756-TAAAAAAAA-TAAAAAAA

Variant names:

• chr7-117504756-TA-T
• rs372341779
• NM_000492.4:c.164+410delA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000492.4(CFTR):​c.164+410delA 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 0.087 (377 hom., cov: 0)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.840
• 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.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0981 is higher than 0.05.

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.164+410delA		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.164+394delA		intron	N/A	ENSP00000003084.6	P13569-1
	CFTR	ENST00000699602.1		c.164+394delA		intron	N/A	ENSP00000514471.1	A0A8V8TNH2
	CFTR	ENST00000889206.1		c.164+394delA		intron	N/A	ENSP00000559265.1

Frequencies

GnomAD3 genomes AF: 0.0872 AC: 10553 AN: 120994 Hom.: 380 Cov.: 0

Gnomad AFR AF: 0.0686

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0894

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.00792

Gnomad SAS AF: 0.0641

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.0872 AC: 10548 AN: 120976 Hom.: 377 Cov.: 0 AF XY: 0.0877 AC XY: 5027 AN XY: 57314

African (AFR) AF: 0.0686 AC: 2373 AN: 34608

American (AMR) AF: 0.0894 AC: 1029 AN: 11504

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 314 AN: 2834

East Asian (EAS) AF: 0.00796 AC: 31 AN: 3896

South Asian (SAS) AF: 0.0642 AC: 228 AN: 3552

European-Finnish (FIN) AF: 0.113 AC: 647 AN: 5740

Middle Eastern (MID) AF: 0.137 AC: 31 AN: 226

European-Non Finnish (NFE) AF: 0.100 AC: 5643 AN: 56246

Other (OTH) AF: 0.104 AC: 167 AN: 1612

Alfa AF: 0.00 Hom.: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.84
Mutation Taster		=100/0	polymorphism (auto)

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: rs372341779; hg19: chr7-117144810;