chr7-117541098-A-G

Variant names:

• chr7-117541098-A-G
• rs2237725
• NM_000492.4:c.1116+752A>G

Variant summary

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

The NM_000492.4(CFTR):​c.1116+752A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,158 control chromosomes in the GnomAD database, including 1,460 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 0.11 (1460 hom., cov: 32)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 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.1116+752A>G		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.1116+752A>G		intron	N/A	ENSP00000003084.6
	CFTR	ENST00000699602.1		c.1116+752A>G		intron	N/A	ENSP00000514471.1
	CFTR	ENST00000426809.5	TSL:5	c.1026+752A>G		intron	N/A	ENSP00000389119.1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16929 AN: 152040 Hom.: 1453 Cov.: 32

Gnomad AFR AF: 0.0740

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.0545

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.0992

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0833

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.111 AC: 16950 AN: 152158 Hom.: 1460 Cov.: 32 AF XY: 0.118 AC XY: 8804 AN XY: 74390

African (AFR) AF: 0.0740 AC: 3073 AN: 41528

American (AMR) AF: 0.209 AC: 3191 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0545 AC: 189 AN: 3470

East Asian (EAS) AF: 0.414 AC: 2136 AN: 5160

South Asian (SAS) AF: 0.290 AC: 1396 AN: 4818

European-Finnish (FIN) AF: 0.0992 AC: 1052 AN: 10604

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0833 AC: 5661 AN: 67974

Other (OTH) AF: 0.101 AC: 214 AN: 2116

Alfa AF: 0.0871 Hom.: 411

Bravo AF: 0.118

Asia WGS AF: 0.361 AC: 1256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.57
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2237725; hg19: chr7-117181152;