rs213989

Variant names:

• chr7-117627457-C-A
• rs213989
• NM_000492.4:c.3469-65C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-117627457-C-A
• chr7-117627457-C-G
• chr7-117627457-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000492.4(CFTR):​c.3469-65C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,543,244 control chromosomes in the GnomAD database, including 29,570 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2761 hom., cov: 32)
  • Exomes 𝑓: 0.19 (26809 hom.)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.115
• Publications: 9 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)

ENSG00000083622 (HGNC:40145):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-117627457-C-A is Benign according to our data. Variant chr7-117627457-C-A is described in ClinVar as Benign. ClinVar VariationId is 818096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4	c.3469-65C>A		intron_variant	Intron 21 of 26	ENST00000003084.11	NP_000483.3
CFTR-AS2	NR_199597.1	n.66-11117G>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11	c.3469-65C>A		intron_variant	Intron 21 of 26	1	NM_000492.4	ENSP00000003084.6

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27886 AN: 151914 Hom.: 2760 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0142

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.179

GnomAD4 exome AF: 0.192 AC: 267179 AN: 1391212 Hom.: 26809 AF XY: 0.193 AC XY: 134207 AN XY: 694544

African (AFR) AF: 0.174 AC: 5579 AN: 32044

American (AMR) AF: 0.115 AC: 5010 AN: 43706

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 3461 AN: 25522

East Asian (EAS) AF: 0.0141 AC: 549 AN: 38974

South Asian (SAS) AF: 0.219 AC: 18194 AN: 83100

European-Finnish (FIN) AF: 0.230 AC: 12039 AN: 52334

Middle Eastern (MID) AF: 0.207 AC: 1068 AN: 5154

European-Non Finnish (NFE) AF: 0.200 AC: 210718 AN: 1052592

Other (OTH) AF: 0.183 AC: 10561 AN: 57786

GnomAD4 genome AF: 0.184 AC: 27899 AN: 152032 Hom.: 2761 Cov.: 32 AF XY: 0.183 AC XY: 13625 AN XY: 74310

African (AFR) AF: 0.172 AC: 7154 AN: 41474

American (AMR) AF: 0.158 AC: 2417 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 456 AN: 3466

East Asian (EAS) AF: 0.0141 AC: 73 AN: 5184

South Asian (SAS) AF: 0.192 AC: 924 AN: 4818

European-Finnish (FIN) AF: 0.233 AC: 2463 AN: 10556

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.204 AC: 13845 AN: 67956

Other (OTH) AF: 0.177 AC: 374 AN: 2112

Alfa AF: 0.201 Hom.: 537

Bravo AF: 0.174

Asia WGS AF: 0.111 AC: 386 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 21, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Cystic fibrosis Benign:1

Jan 29, 2018

CFTR-France

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

the variant does not result in CFTR-RD neither -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.5
DANN	Benign	0.44
PhyloP100		-0.12
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: rs213989; hg19: chr7-117267511;