rs397507565

Variant names:

• chr7-117479600-C-T
• rs397507565
• ENST00000546407.1:n.166+3792C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000546407.1(CFTR):​n.166+3792C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CFTR ENST00000546407.1 intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -6.94
• 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: 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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	ENST00000546407.1	n.166+3792C>T		intron_variant	Intron 2 of 2	1
CFTR	ENST00000446805.2	c.-285C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 3 of 6	4		ENSP00000417012.1
CFTR	ENST00000446805.2	c.-285C>T		5_prime_UTR_variant	Exon 3 of 6	4		ENSP00000417012.1
CFTR	ENST00000673785.1	c.-406+13769C>T		intron_variant	Intron 3 of 12			ENSP00000501235.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 25080 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 12986

African (AFR) AF: 0.00 AC: 0 AN: 580

American (AMR) AF: 0.00 AC: 0 AN: 2804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 468

East Asian (EAS) AF: 0.00 AC: 0 AN: 1488

South Asian (SAS) AF: 0.00 AC: 0 AN: 3148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 728

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 96

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 14432

Other (OTH) AF: 0.00 AC: 0 AN: 1336

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Cystic fibrosis Uncertain:1

Sep 28, 2017

Counsyl

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.35
DANN	Benign	0.57
PhyloP100		-6.9
PromoterAI		0.024	Neutral

Splicing

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

Other links and lift over

dbSNP: rs397507565; hg19: chr7-117119654;