chr7-117548606-A-ATG

Variant names:

• chr7-117548606-A-ATG
• rs3832534
• NM_000492.4:c.1210-13_1210-12dupGT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000492.4(CFTR):​c.1210-13_1210-12dupGT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.13 (1779 hom., cov: 0)
  • Exomes 𝑓: 0.12 (2389 hom.)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6 O:1
• Conservation: PhyloP100: 0.0650

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

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 7-117548606-A-ATG is Benign according to our data. Variant chr7-117548606-A-ATG is described in ClinVar as [Benign]. Clinvar id is 229652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4	c.1210-13_1210-12dupGT		intron_variant	Intron 9 of 26	ENST00000003084.11	NP_000483.3
CFTR-AS1	NR_149084.1	n.222-6069_222-6068dupCA		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11	c.1210-35_1210-34insTG		intron_variant	Intron 9 of 26	1	NM_000492.4	ENSP00000003084.6

Frequencies

GnomAD3 genomes AF: 0.130 AC: 18711 AN: 143394 Hom.: 1778 Cov.: 0

Gnomad AFR AF: 0.0789

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.0911

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0725

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.126

GnomAD2 exomes AF: 0.199 AC: 35369 AN: 177682 AF XY: 0.195

Gnomad AFR exome AF: 0.0828

Gnomad AMR exome AF: 0.341

Gnomad ASJ exome AF: 0.125

Gnomad EAS exome AF: 0.429

Gnomad FIN exome AF: 0.124

Gnomad NFE exome AF: 0.117

Gnomad OTH exome AF: 0.186

GnomAD4 exome AF: 0.121 AC: 164900 AN: 1367614 Hom.: 2389 Cov.: 0 AF XY: 0.123 AC XY: 83442 AN XY: 679818

African (AFR) AF: 0.0762 AC: 2411 AN: 31634

American (AMR) AF: 0.290 AC: 11895 AN: 41044

Ashkenazi Jewish (ASJ) AF: 0.0889 AC: 2131 AN: 23970

East Asian (EAS) AF: 0.383 AC: 14048 AN: 36698

South Asian (SAS) AF: 0.232 AC: 18683 AN: 80442

European-Finnish (FIN) AF: 0.104 AC: 5135 AN: 49558

Middle Eastern (MID) AF: 0.0783 AC: 424 AN: 5412

European-Non Finnish (NFE) AF: 0.0985 AC: 102668 AN: 1042584

Other (OTH) AF: 0.133 AC: 7505 AN: 56272

GnomAD4 genome AF: 0.131 AC: 18730 AN: 143494 Hom.: 1779 Cov.: 0 AF XY: 0.137 AC XY: 9537 AN XY: 69734

African (AFR) AF: 0.0788 AC: 3104 AN: 39366

American (AMR) AF: 0.239 AC: 3470 AN: 14530

Ashkenazi Jewish (ASJ) AF: 0.0911 AC: 300 AN: 3292

East Asian (EAS) AF: 0.502 AC: 2430 AN: 4842

South Asian (SAS) AF: 0.304 AC: 1349 AN: 4438

European-Finnish (FIN) AF: 0.118 AC: 1093 AN: 9230

Middle Eastern (MID) AF: 0.0709 AC: 18 AN: 254

European-Non Finnish (NFE) AF: 0.103 AC: 6688 AN: 64736

Other (OTH) AF: 0.127 AC: 252 AN: 1992

Alfa AF: 0.0699 Hom.: 240

ClinVar

Significance: Benign

Submissions summary: Benign:6 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2 Other:1

Mar 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Nov 30, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

Variant classified as Benign and reported on 01-24-2023 by Next Genetic Center. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Cystic fibrosis Benign:2

Dec 17, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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 -

not specified Benign:1

May 25, 2018

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1210-34TG[12]T[7] allele in intron 9 of the CFTR gene is classified as be nign because it has been identified in 43% (6544/15040) of East Asian chromosome s in the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs3832534). 930 homozygotes have also been identfied in the gnomAD databas e. ACMG/AMP Criteria applied: BA1 -

Cystic fibrosis;C0238339:Hereditary pancreatitis;C0403814:Congenital bilateral aplasia of vas deferens from CFTR mutation;C2749757:Bronchiectasis with or without elevated sweat chloride 1 Benign:1

Dec 26, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.065
La Branchor		0.64
BranchPoint Hunter		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3832534; hg19: chr7-117188660;