rs3808185

Variant names:

• chr7-117574035-T-C
• rs3808185
• NM_000492.4:c.1585-13704T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-117574035-T-C
• chr7-117574035-T-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.1585-13704T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 151,964 control chromosomes in the GnomAD database, including 3,123 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 0.19 (3123 hom., cov: 32)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.407
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 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.1585-13704T>C		intron	N/A	NP_000483.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFTR	ENST00000003084.11	TSL:1 MANE Select	c.1585-13704T>C		intron	N/A	ENSP00000003084.6	P13569-1
	CFTR	ENST00000699602.1		c.1585-13704T>C		intron	N/A	ENSP00000514471.1	A0A8V8TNH2
	CFTR	ENST00000889206.1		c.1585-13704T>C		intron	N/A	ENSP00000559265.1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28062 AN: 151846 Hom.: 3113 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.0580

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.185 AC: 28117 AN: 151964 Hom.: 3123 Cov.: 32 AF XY: 0.194 AC XY: 14424 AN XY: 74254

African (AFR) AF: 0.254 AC: 10531 AN: 41468

American (AMR) AF: 0.237 AC: 3620 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0580 AC: 201 AN: 3464

East Asian (EAS) AF: 0.416 AC: 2143 AN: 5150

South Asian (SAS) AF: 0.321 AC: 1542 AN: 4804

European-Finnish (FIN) AF: 0.204 AC: 2160 AN: 10572

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7537 AN: 67926

Other (OTH) AF: 0.155 AC: 328 AN: 2114

Alfa AF: 0.123 Hom.: 2119

Bravo AF: 0.189

Asia WGS AF: 0.409 AC: 1423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.5
DANN	Benign	0.68
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

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: rs3808185; hg19: chr7-117214089;