rs1389547129

Variant names:

• chr7-117612035-A-ATG
• rs1389547129
• NM_000492.4:c.3367+228_3367+229insGT

Your query was ambiguous. Multiple possible variants found:

• chr7-117612035-A-ATG
• chr7-117612035-A-ATGTG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000492.4(CFTR):​c.3367+228_3367+229insGT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00030 (1 hom., cov: 12)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138
• 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 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)

ENSG00000083622 (HGNC:40145):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.3367+228_3367+229insGT		intron	N/A	NP_000483.3
	CFTR-AS2	NR_199597.1		n.177+4193_177+4194insCA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFTR	ENST00000003084.11	TSL:1 MANE Select	c.3367+227_3367+228insTG		intron	N/A	ENSP00000003084.6	P13569-1
	CFTR	ENST00000699602.1		c.3367+227_3367+228insTG		intron	N/A	ENSP00000514471.1	A0A8V8TNH2
	CFTR	ENST00000889206.1		c.3280+227_3280+228insTG		intron	N/A	ENSP00000559265.1

Frequencies

GnomAD3 genomes AF: 0.000296 AC: 22 AN: 74244 Hom.: 1 Cov.: 12

Gnomad AFR AF: 0.000122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000248

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000472

Gnomad OTH AF: 0.000996

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

GnomAD4 genome AF: 0.000296 AC: 22 AN: 74236 Hom.: 1 Cov.: 12 AF XY: 0.000197 AC XY: 7 AN XY: 35452

African (AFR) AF: 0.000122 AC: 2 AN: 16418

American (AMR) AF: 0.000248 AC: 2 AN: 8072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2298

East Asian (EAS) AF: 0.00 AC: 0 AN: 3780

South Asian (SAS) AF: 0.00 AC: 0 AN: 2620

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 166

European-Non Finnish (NFE) AF: 0.000472 AC: 17 AN: 36032

Other (OTH) AF: 0.000990 AC: 1 AN: 1010

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.14

Splicing

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

Other links and lift over

dbSNP: rs1389547129; hg19: chr7-117252089;