7-117323508-T-C

Variant names:

• chr7-117323508-T-C
• rs39315
• ENST00000673785.1:c.-491+22478T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000673785.1(CFTR):​c.-491+22478T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 151,992 control chromosomes in the GnomAD database, including 14,727 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (14727 hom., cov: 32)
• Consequence: CFTR ENST00000673785.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.504
• Publications: 11 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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Orphanet
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000673785.1	c.-491+22478T>C		intron_variant	Intron 2 of 12			ENSP00000501235.1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65659 AN: 151874 Hom.: 14697 Cov.: 32

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.433 AC: 65744 AN: 151992 Hom.: 14727 Cov.: 32 AF XY: 0.437 AC XY: 32429 AN XY: 74284

African (AFR) AF: 0.543 AC: 22519 AN: 41466

American (AMR) AF: 0.456 AC: 6975 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 845 AN: 3472

East Asian (EAS) AF: 0.424 AC: 2175 AN: 5128

South Asian (SAS) AF: 0.551 AC: 2659 AN: 4826

European-Finnish (FIN) AF: 0.416 AC: 4394 AN: 10550

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24959 AN: 67952

Other (OTH) AF: 0.414 AC: 876 AN: 2114

Alfa AF: 0.336 Hom.: 1350

Bravo AF: 0.435

Asia WGS AF: 0.529 AC: 1843 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.0
DANN	Benign	0.61
PhyloP100		-0.50
PromoterAI		-0.078	Neutral

Splicing

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

Other links and lift over

dbSNP: rs39315; hg19: chr7-116963562;