chr7-117538700-A-G

Position:

• chr7-117538700-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000003084.11(CFTR):​c.870-1400A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0916 in 152,178 control chromosomes in the GnomAD database, including 824 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 0.092 (824 hom., cov: 32)
• Consequence: CFTR ENST00000003084.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFTR	NM_000492.4	c.870-1400A>G		intron_variant		ENST00000003084.11	NP_000483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11	c.870-1400A>G		intron_variant		1	NM_000492.4	ENSP00000003084	P2

Frequencies

GnomAD3 genomes AF: 0.0917 AC: 13949 AN: 152060 Hom.: 825 Cov.: 32

Gnomad AFR AF: 0.0286

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0530

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0599

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.0916 AC: 13944 AN: 152178 Hom.: 824 Cov.: 32 AF XY: 0.0919 AC XY: 6839 AN XY: 74400

Gnomad4 AFR AF: 0.0286

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.0530

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0592

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.104

Alfa AF: 0.117 Hom.: 1111

Bravo AF: 0.0827

Asia WGS AF: 0.0310 AC: 108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.049
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs17449197; hg19: chr7-117178754;