rs965265631

Variant names:

• chr7-117633643-GT-G
• rs965265631
• NM_000492.4:c.3717+5885delT

Your query was ambiguous. Multiple possible variants found:

• chr7-117633643-GT-G
• chr7-117633643-GT-GTT
• chr7-117633643-GT-GTTT

Variant summary

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

The NM_000492.4(CFTR):​c.3717+5885delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00517 in 145,066 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0052 (1 hom., cov: 32)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.955
• 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.3717+5885delT		intron	N/A	NP_000483.3
	CFTR-AS2	NR_199597.1		n.65+13707delA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFTR	ENST00000003084.11	TSL:1 MANE Select	c.3717+5874delT		intron	N/A	ENSP00000003084.6	P13569-1
	CFTR	ENST00000699602.1		c.3711+5874delT		intron	N/A	ENSP00000514471.1	A0A8V8TNH2
	CFTR	ENST00000889206.1		c.3630+5874delT		intron	N/A	ENSP00000559265.1

Frequencies

GnomAD3 genomes AF: 0.00515 AC: 747 AN: 145018 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00582

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00344

Gnomad ASJ AF: 0.00119

Gnomad EAS AF: 0.000398

Gnomad SAS AF: 0.000432

Gnomad FIN AF: 0.00334

Gnomad MID AF: 0.0267

Gnomad NFE AF: 0.00622

Gnomad OTH AF: 0.00609

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

GnomAD4 genome AF: 0.00517 AC: 750 AN: 145066 Hom.: 1 Cov.: 32 AF XY: 0.00481 AC XY: 339 AN XY: 70522

African (AFR) AF: 0.00591 AC: 236 AN: 39952

American (AMR) AF: 0.00337 AC: 49 AN: 14544

Ashkenazi Jewish (ASJ) AF: 0.00119 AC: 4 AN: 3362

East Asian (EAS) AF: 0.000400 AC: 2 AN: 5006

South Asian (SAS) AF: 0.000650 AC: 3 AN: 4614

European-Finnish (FIN) AF: 0.00334 AC: 30 AN: 8976

Middle Eastern (MID) AF: 0.0217 AC: 6 AN: 276

European-Non Finnish (NFE) AF: 0.00622 AC: 407 AN: 65452

Other (OTH) AF: 0.00655 AC: 13 AN: 1984

Alfa AF: 0.000218 Hom.: 0

Bravo AF: 0.00484

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.95
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: rs965265631; hg19: chr7-117273697;