7-117545823-A-AT

Variant names:

• chr7-117545823-A-AT
• rs142583564
• NM_000492.4:c.1210-2809dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000492.4(CFTR):​c.1210-2809dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00794 in 149,832 control chromosomes in the GnomAD database, including 36 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0079 (36 hom., cov: 32)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284
• 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-AS1 (HGNC:40144): (CFTR antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0895 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFTR	NM_000492.4	MANE Select	c.1210-2809dupT		intron	N/A	NP_000483.3
	CFTR-AS1	NR_149084.1		n.222-3285dupA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFTR	ENST00000003084.11	TSL:1 MANE Select	c.1210-2818_1210-2817insT		intron	N/A	ENSP00000003084.6	P13569-1
	CFTR	ENST00000699602.1		c.1210-2818_1210-2817insT		intron	N/A	ENSP00000514471.1	A0A8V8TNH2
	CFTR	ENST00000889206.1		c.1210-2818_1210-2817insT		intron	N/A	ENSP00000559265.1

Frequencies

GnomAD3 genomes AF: 0.00794 AC: 1189 AN: 149714 Hom.: 36 Cov.: 32

Gnomad AFR AF: 0.00148

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0970

Gnomad SAS AF: 0.00828

Gnomad FIN AF: 0.00724

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00375

Gnomad OTH AF: 0.00731

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

GnomAD4 genome AF: 0.00794 AC: 1189 AN: 149832 Hom.: 36 Cov.: 32 AF XY: 0.00858 AC XY: 627 AN XY: 73074

African (AFR) AF: 0.00147 AC: 60 AN: 40732

American (AMR) AF: 0.0171 AC: 257 AN: 15034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3430

East Asian (EAS) AF: 0.0966 AC: 489 AN: 5062

South Asian (SAS) AF: 0.00808 AC: 38 AN: 4702

European-Finnish (FIN) AF: 0.00724 AC: 74 AN: 10218

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.00375 AC: 253 AN: 67386

Other (OTH) AF: 0.00723 AC: 15 AN: 2074

Alfa AF: 0.00142 Hom.: 0

Asia WGS AF: 0.0550 AC: 190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism

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: rs142583564; hg19: chr7-117185877;