rs713134

Variant names:

• chr7-117475202-C-T
• rs713134
• ENST00000546407.1:n.49-489C>T

Variant summary

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

The ENST00000546407.1(CFTR):​n.49-489C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 151,980 control chromosomes in the GnomAD database, including 27,986 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 0.57 (27986 hom., cov: 32)
• Consequence: CFTR ENST00000546407.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.586
• Publications: 3 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)

LOC105375468 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105375468	XR_927901.2	n.228-489C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000546407.1	n.49-489C>T		intron_variant	Intron 1 of 2	1
CFTR	ENST00000673785.1	c.-406+9371C>T		intron_variant	Intron 3 of 12			ENSP00000501235.1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86616 AN: 151862 Hom.: 27920 Cov.: 32

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.571 AC: 86744 AN: 151980 Hom.: 27986 Cov.: 32 AF XY: 0.576 AC XY: 42753 AN XY: 74260

African (AFR) AF: 0.886 AC: 36785 AN: 41506

American (AMR) AF: 0.529 AC: 8068 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 984 AN: 3472

East Asian (EAS) AF: 0.459 AC: 2369 AN: 5156

South Asian (SAS) AF: 0.582 AC: 2798 AN: 4810

European-Finnish (FIN) AF: 0.564 AC: 5938 AN: 10532

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28290 AN: 67926

Other (OTH) AF: 0.525 AC: 1107 AN: 2110

Alfa AF: 0.527 Hom.: 2931

Bravo AF: 0.578

Asia WGS AF: 0.583 AC: 2028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	6.2
DANN	Benign	0.60
PhyloP100		0.59

Splicing

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

Other links and lift over

dbSNP: rs713134; hg19: chr7-117115256;