7-117579781-C-T

Variant names:

• chr7-117579781-C-T
• rs1469486
• NM_000492.4:c.1585-7958C>T

Variant summary

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

The NM_000492.4(CFTR):​c.1585-7958C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 150,028 control chromosomes in the GnomAD database, including 2,802 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 0.18 (2802 hom., cov: 31)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222
• Publications: 6 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFTR	NM_000492.4	MANE Select	c.1585-7958C>T		intron	N/A	NP_000483.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFTR	ENST00000003084.11	TSL:1 MANE Select	c.1585-7958C>T		intron	N/A	ENSP00000003084.6
	CFTR	ENST00000699602.1		c.1585-7958C>T		intron	N/A	ENSP00000514471.1
	CFTR	ENST00000426809.5	TSL:5	c.1495-7958C>T		intron	N/A	ENSP00000389119.1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26588 AN: 149940 Hom.: 2792 Cov.: 31

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.0352

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.0597

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.0673

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.178 AC: 26638 AN: 150028 Hom.: 2802 Cov.: 31 AF XY: 0.188 AC XY: 13722 AN XY: 73122

African (AFR) AF: 0.225 AC: 9200 AN: 40928

American (AMR) AF: 0.238 AC: 3577 AN: 15052

Ashkenazi Jewish (ASJ) AF: 0.0597 AC: 206 AN: 3448

East Asian (EAS) AF: 0.420 AC: 2144 AN: 5100

South Asian (SAS) AF: 0.324 AC: 1545 AN: 4766

European-Finnish (FIN) AF: 0.211 AC: 2116 AN: 10044

Middle Eastern (MID) AF: 0.0694 AC: 20 AN: 288

European-Non Finnish (NFE) AF: 0.111 AC: 7488 AN: 67424

Other (OTH) AF: 0.150 AC: 310 AN: 2070

Alfa AF: 0.135 Hom.: 554

Bravo AF: 0.180

Asia WGS AF: 0.398 AC: 1369 AN: 3438

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.63
DANN	Benign	0.46
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1469486; hg19: chr7-117219835;