chr7-117548606-ATG-A

Variant names:

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

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_1210-12delGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,335,714 control chromosomes in the GnomAD database, including 17,978 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.26 (5655 hom., cov: 0)
  • Exomes 𝑓: 0.20 (12323 hom.)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.0750
• Publications: 2 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-AS1 (HGNC:40144): (CFTR antisense RNA 1)

ACMG classification

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

• BP6: Variant 7-117548606-ATG-A is Benign according to our data. Variant chr7-117548606-ATG-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 439475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFTR	NM_000492.4	MANE Select	c.1210-13_1210-12delGT		intron	N/A	NP_000483.3
	CFTR-AS1	NR_149084.1		n.222-6069_222-6068delCA		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFTR	ENST00000003084.11	TSL:1 MANE Select	c.1210-34_1210-33delTG		intron	N/A	ENSP00000003084.6
	CFTR	ENST00000699602.1		c.1210-34_1210-33delTG		intron	N/A	ENSP00000514471.1
	CFTR	ENST00000426809.5	TSL:5	c.1120-34_1120-33delTG		intron	N/A	ENSP00000389119.1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 36639 AN: 143230 Hom.: 5641 Cov.: 0

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.00103

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.236

GnomAD2 exomes AF: 0.222 AC: 39472 AN: 177682 AF XY: 0.225

Gnomad AFR exome AF: 0.438

Gnomad AMR exome AF: 0.144

Gnomad ASJ exome AF: 0.159

Gnomad EAS exome AF: 0.0237

Gnomad FIN exome AF: 0.260

Gnomad NFE exome AF: 0.270

Gnomad OTH exome AF: 0.223

GnomAD4 exome AF: 0.205 AC: 244096 AN: 1192382 Hom.: 12323 AF XY: 0.204 AC XY: 120680 AN XY: 591510

African (AFR) AF: 0.422 AC: 13019 AN: 30818

American (AMR) AF: 0.147 AC: 5570 AN: 37880

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 2866 AN: 19082

East Asian (EAS) AF: 0.0186 AC: 621 AN: 33366

South Asian (SAS) AF: 0.149 AC: 10378 AN: 69468

European-Finnish (FIN) AF: 0.250 AC: 11099 AN: 44428

Middle Eastern (MID) AF: 0.219 AC: 1034 AN: 4722

European-Non Finnish (NFE) AF: 0.210 AC: 189421 AN: 903470

Other (OTH) AF: 0.205 AC: 10088 AN: 49148

GnomAD4 genome AF: 0.256 AC: 36691 AN: 143332 Hom.: 5655 Cov.: 0 AF XY: 0.252 AC XY: 17562 AN XY: 69656

African (AFR) AF: 0.459 AC: 18035 AN: 39292

American (AMR) AF: 0.193 AC: 2809 AN: 14530

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 338 AN: 3286

East Asian (EAS) AF: 0.00103 AC: 5 AN: 4846

South Asian (SAS) AF: 0.108 AC: 478 AN: 4438

European-Finnish (FIN) AF: 0.250 AC: 2303 AN: 9194

Middle Eastern (MID) AF: 0.202 AC: 51 AN: 252

European-Non Finnish (NFE) AF: 0.187 AC: 12108 AN: 64694

Other (OTH) AF: 0.233 AC: 462 AN: 1986

Alfa AF: 0.171 Hom.: 240

Bravo AF: 0.251

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Mar 17, 2018

GeneDx

Significance: Benign

Review Status: flagged submission

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.

Apr 29, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

c.1210-14_1210-13delTG in intron 9 of CFTR: This variant is not expected to have clinical significance because it has been identified in 47% (582/3375) of Afric an chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinsti tute.org; dbSNP rs3832534).

Cystic fibrosis Benign:2

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

Dec 17, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Nov 30, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Dec 27, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Inborn genetic diseases Benign:1

Oct 11, 2018

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Other strong data

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.075
La Branchor		0.64
BranchPoint Hunter		2.0
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: rs3832534; hg19: chr7-117188660;