NM_000492.4:c.164+410dupA

Variant names:

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

Variant summary

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

The NM_000492.4(CFTR):​c.164+410dupA 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 0.14 (3377 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 (AFR) allele frequency at 95% confidence interval = 0.433 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+410dupA		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+393_164+394insA		intron	N/A	ENSP00000003084.6	P13569-1
	CFTR	ENST00000699602.1		c.164+393_164+394insA		intron	N/A	ENSP00000514471.1	A0A8V8TNH2
	CFTR	ENST00000889206.1		c.164+393_164+394insA		intron	N/A	ENSP00000559265.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 17178 AN: 121038 Hom.: 3375 Cov.: 0

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.00132

Gnomad AMR AF: 0.0590

Gnomad ASJ AF: 0.0489

Gnomad EAS AF: 0.0412

Gnomad SAS AF: 0.0134

Gnomad FIN AF: 0.00314

Gnomad MID AF: 0.103

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.142 AC: 17192 AN: 121020 Hom.: 3377 Cov.: 0 AF XY: 0.139 AC XY: 7958 AN XY: 57334

African (AFR) AF: 0.439 AC: 15189 AN: 34582

American (AMR) AF: 0.0589 AC: 678 AN: 11512

Ashkenazi Jewish (ASJ) AF: 0.0489 AC: 139 AN: 2840

East Asian (EAS) AF: 0.0413 AC: 161 AN: 3894

South Asian (SAS) AF: 0.0135 AC: 48 AN: 3554

European-Finnish (FIN) AF: 0.00314 AC: 18 AN: 5740

Middle Eastern (MID) AF: 0.110 AC: 25 AN: 228

European-Non Finnish (NFE) AF: 0.0129 AC: 724 AN: 56304

Other (OTH) AF: 0.130 AC: 209 AN: 1608

Alfa AF: 0.00824 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;