7-117479129-T-G

Variant names:

• chr7-117479129-T-G
• rs4148682
• ENST00000546407.1:n.166+3321T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000546407.1(CFTR):​n.166+3321T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,134 control chromosomes in the GnomAD database, including 1,560 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (1560 hom., cov: 32)
• Consequence: CFTR ENST00000546407.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.260
• Publications: 15 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 7-117479129-T-G is Benign according to our data. Variant chr7-117479129-T-G is described in ClinVar as Benign. ClinVar VariationId is 818101.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 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	ENST00000546407.1	n.166+3321T>G		intron_variant	Intron 2 of 2	1
CFTR	ENST00000673785.1	c.-406+13298T>G		intron_variant	Intron 3 of 12			ENSP00000501235.1
CFTR	ENST00000446805.2	c.-525-115T>G		intron_variant	Intron 1 of 5	4		ENSP00000417012.1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16945 AN: 152018 Hom.: 1553 Cov.: 32

Gnomad AFR AF: 0.0674

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.0545

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0835

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.112 AC: 16968 AN: 152134 Hom.: 1560 Cov.: 32 AF XY: 0.119 AC XY: 8840 AN XY: 74354

African (AFR) AF: 0.0674 AC: 2799 AN: 41538

American (AMR) AF: 0.209 AC: 3191 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0545 AC: 189 AN: 3468

East Asian (EAS) AF: 0.464 AC: 2386 AN: 5138

South Asian (SAS) AF: 0.293 AC: 1412 AN: 4816

European-Finnish (FIN) AF: 0.100 AC: 1063 AN: 10582

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0835 AC: 5678 AN: 68004

Other (OTH) AF: 0.100 AC: 211 AN: 2108

Alfa AF: 0.0873 Hom.: 501

Bravo AF: 0.118

Asia WGS AF: 0.376 AC: 1308 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cystic fibrosis Benign:1

Jul 17, 2015

CFTR-France

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

the variant does not result in CFTR-RD neither -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.1
DANN	Benign	0.72
PhyloP100		-0.26

Splicing

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

Other links and lift over

dbSNP: rs4148682; hg19: chr7-117119183;