7-117504756-TAAAAAAAA-TAAAAAAAAAA

Variant names:

• chr7-117504756-T-TAA
• rs372341779
• NM_000492.4:c.164+409_164+410dupAA

Variant summary

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

The NM_000492.4(CFTR):​c.164+409_164+410dupAA 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 0.19 (2047 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 = 0.212 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+409_164+410dupAA		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+394insAA		intron	N/A	ENSP00000003084.6	P13569-1
	CFTR	ENST00000699602.1		c.164+393_164+394insAA		intron	N/A	ENSP00000514471.1	A0A8V8TNH2
	CFTR	ENST00000889206.1		c.164+393_164+394insAA		intron	N/A	ENSP00000559265.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 22418 AN: 120798 Hom.: 2047 Cov.: 0

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.000767

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.163

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.186 AC: 22418 AN: 120780 Hom.: 2047 Cov.: 0 AF XY: 0.184 AC XY: 10513 AN XY: 57194

African (AFR) AF: 0.167 AC: 5768 AN: 34556

American (AMR) AF: 0.173 AC: 1980 AN: 11474

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 309 AN: 2836

East Asian (EAS) AF: 0.000770 AC: 3 AN: 3894

South Asian (SAS) AF: 0.123 AC: 435 AN: 3544

European-Finnish (FIN) AF: 0.243 AC: 1385 AN: 5700

Middle Eastern (MID) AF: 0.158 AC: 36 AN: 228

European-Non Finnish (NFE) AF: 0.215 AC: 12088 AN: 56182

Other (OTH) AF: 0.177 AC: 285 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

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs372341779; hg19: chr7-117144810;