rs2283058

Variant names:

• chr7-117662856-A-C
• rs2283058
• NM_000492.4:c.3964-1832A>C

Your query was ambiguous. Multiple possible variants found:

• chr7-117662856-A-C
• chr7-117662856-A-G
• chr7-117662856-A-T

Variant summary

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

The NM_000492.4(CFTR):​c.3964-1832A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,126 control chromosomes in the GnomAD database, including 2,160 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 0.15 (2160 hom., cov: 32)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.972
• 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: 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4	c.3964-1832A>C		intron_variant	Intron 24 of 26	ENST00000003084.11	NP_000483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11	c.3964-1832A>C		intron_variant	Intron 24 of 26	1	NM_000492.4	ENSP00000003084.6

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22839 AN: 152008 Hom.: 2148 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.0885

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.0632

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0935

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.150 AC: 22874 AN: 152126 Hom.: 2160 Cov.: 32 AF XY: 0.150 AC XY: 11181 AN XY: 74376

African (AFR) AF: 0.242 AC: 10056 AN: 41474

American (AMR) AF: 0.171 AC: 2615 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0885 AC: 307 AN: 3470

East Asian (EAS) AF: 0.313 AC: 1612 AN: 5152

South Asian (SAS) AF: 0.177 AC: 853 AN: 4810

European-Finnish (FIN) AF: 0.0632 AC: 671 AN: 10612

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0935 AC: 6359 AN: 68004

Other (OTH) AF: 0.133 AC: 280 AN: 2112

Alfa AF: 0.0568 Hom.: 85

Bravo AF: 0.167

Asia WGS AF: 0.255 AC: 889 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.26
DANN	Benign	0.55
PhyloP100		-0.97
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: rs2283058; hg19: chr7-117302910;