chr7-117479930-G-A

Variant names:

• chr7-117479930-G-A
• rs145483167
• ENST00000546407.1:n.166+4122G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000446805.2(CFTR):​c.-191+236G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 734,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: CFTR ENST00000446805.2 intron
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:6
• Conservation: PhyloP100: 0.167
• Publications: 1 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: Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Laboratory for Molecular Medicine
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000446805.2. 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.-165G>A		upstream_gene	N/A	NP_000483.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFTR	ENST00000546407.1	TSL:1	n.166+4122G>A		intron	N/A
	CFTR	ENST00000673785.1		c.-406+14099G>A		intron	N/A	ENSP00000501235.1	A0A669KBE8
	CFTR	ENST00000446805.2	TSL:4	c.-191+236G>A		intron	N/A	ENSP00000417012.1	C9J6L5

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 151750 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000592

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000111 AC: 65 AN: 583226 Hom.: 0 Cov.: 6 AF XY: 0.0000853 AC XY: 27 AN XY: 316578

African (AFR) AF: 0.0000600 AC: 1 AN: 16654

American (AMR) AF: 0.000813 AC: 32 AN: 39366

Ashkenazi Jewish (ASJ) AF: 0.000369 AC: 7 AN: 18986

East Asian (EAS) AF: 0.00 AC: 0 AN: 35396

South Asian (SAS) AF: 0.000154 AC: 10 AN: 65090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2322

European-Non Finnish (NFE) AF: 0.0000266 AC: 9 AN: 337956

Other (OTH) AF: 0.000191 AC: 6 AN: 31338

GnomAD4 genome AF: 0.000105 AC: 16 AN: 151750 Hom.: 0 Cov.: 29 AF XY: 0.000108 AC XY: 8 AN XY: 74106

African (AFR) AF: 0.00 AC: 0 AN: 41280

American (AMR) AF: 0.000592 AC: 9 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000589 AC: 4 AN: 67952

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	3	-	not provided (3)
-	2	-	Cystic fibrosis (2)
-	1	-	CFTR-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Benign	0.65
PhyloP100		0.17
PromoterAI		-0.051	Neutral

Splicing

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

Other links and lift over

dbSNP: rs145483167; hg19: chr7-117119984;