dbSNP rs3832534: CFTR:c.1210-19_1210-12delGTGTGTGT (chr7-117548606-ATGTGTGTG-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_000492.4(CFTR):c.1210-19_1210-12delGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (no stars). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CFTR
NM_000492.4 intron

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.46

Publications

2 publications found

Variant links:

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 links:

CFTR-AS1 (HGNC:40144): (CFTR antisense RNA 1)

CFTR-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP6

Variant 7-117548606-ATGTGTGTG-A is Benign according to our data. Variant chr7-117548606-ATGTGTGTG-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3029545.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4 link	c.1210-19_1210-12delGTGTGTGT		intron_variant	Intron 9 of 26	ENST00000003084.11	NP_000483.3
CFTR-AS1	NR_149084.1 link	n.222-6075_222-6068delCACACACA		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11 link	c.1210-34_1210-27delTGTGTGTG		intron_variant	Intron 9 of 26	1	NM_000492.4	ENSP00000003084.6

Frequencies

GnomAD3 genomes

AF:

0.0000139

AC:

AN:

143508

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000255

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000154

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000190

AC:

AN:

1370532

Hom.:

AF XY:

0.0000220

AC XY:

AN XY:

681290

show subpopulations

African (AFR)

AF:

0.0000316

AC:

AN:

31670

American (AMR)

AF:

0.00

AC:

AN:

41254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24034

East Asian (EAS)

AF:

0.0000543

AC:

AN:

36852

South Asian (SAS)

AF:

0.00

AC:

AN:

80646

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49644

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5422

European-Non Finnish (NFE)

AF:

0.0000220

AC:

AN:

1044602

Other (OTH)

AF:

0.00

AC:

AN:

56408

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.413

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000139

AC:

AN:

143508

Hom.:

Cov.:

AF XY:

0.0000144

AC XY:

AN XY:

69684

show subpopulations

African (AFR)

AF:

0.0000255

AC:

AN:

39280

American (AMR)

AF:

0.00

AC:

AN:

14530

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3294

East Asian (EAS)

AF:

0.00

AC:

AN:

4860

South Asian (SAS)

AF:

0.00

AC:

AN:

4456

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9248

Middle Eastern (MID)

AF:

0.00

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.0000154

AC:

AN:

64778

Other (OTH)

AF:

0.00

AC:

AN:

1972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

240

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CFTR-related disorder

Benign:1

Nov 18, 2021

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.5

La Branchor

0.64

BranchPoint Hunter

2.0

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over