7-117504756-TAAAAAAAA-TAAAAAAAAAAA

Variant names:

• chr7-117504756-T-TAAA
• rs372341779
• NM_000492.4:c.164+408_164+410dupAAA

Variant summary

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

The NM_000492.4(CFTR):​c.164+408_164+410dupAAA 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 0.020 (32 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.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0197 (2388/121040) while in subpopulation AFR AF = 0.0242 (839/34618). AF 95% confidence interval is 0.0229. There are 32 homozygotes in GnomAd4. There are 1064 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 32 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.164+408_164+410dupAAA		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+394insAAA		intron	N/A	ENSP00000003084.6	P13569-1
	CFTR	ENST00000699602.1		c.164+393_164+394insAAA		intron	N/A	ENSP00000514471.1	A0A8V8TNH2
	CFTR	ENST00000889206.1		c.164+393_164+394insAAA		intron	N/A	ENSP00000559265.1

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 2390 AN: 121058 Hom.: 32 Cov.: 0

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.0437

Gnomad AMR AF: 0.0181

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00280

Gnomad FIN AF: 0.00662

Gnomad MID AF: 0.0317

Gnomad NFE AF: 0.0211

Gnomad OTH AF: 0.0180

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

GnomAD4 genome AF: 0.0197 AC: 2388 AN: 121040 Hom.: 32 Cov.: 0 AF XY: 0.0186 AC XY: 1064 AN XY: 57340

African (AFR) AF: 0.0242 AC: 839 AN: 34618

American (AMR) AF: 0.0181 AC: 208 AN: 11504

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 37 AN: 2840

East Asian (EAS) AF: 0.00 AC: 0 AN: 3896

South Asian (SAS) AF: 0.00253 AC: 9 AN: 3554

European-Finnish (FIN) AF: 0.00662 AC: 38 AN: 5740

Middle Eastern (MID) AF: 0.0351 AC: 8 AN: 228

European-Non Finnish (NFE) AF: 0.0211 AC: 1187 AN: 56290

Other (OTH) AF: 0.0180 AC: 29 AN: 1614

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

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;