7-117548606-ATGTGTGTG-ATGTGTGTGTGTG

Variant names:

• chr7-117548606-A-ATGTG
• rs3832534
• NM_000492.4:c.1210-15_1210-12dupGTGT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_000492.4(CFTR):​c.1210-15_1210-12dupGTGT 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 0.00091 (1 hom., cov: 0)
  • Exomes 𝑓: 0.00087 (0 hom.)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0650
• 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 -8 ACMG points.

• BP6: Variant 7-117548606-A-ATGTG is Benign according to our data. Variant chr7-117548606-A-ATGTG is described in ClinVar as Benign. ClinVar VariationId is 496577.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.1210-15_1210-12dupGTGT		intron	N/A	NP_000483.3
	CFTR-AS1	NR_149084.1		n.222-6071_222-6068dupCACA		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFTR	ENST00000003084.11	TSL:1 MANE Select	c.1210-35_1210-34insTGTG		intron	N/A	ENSP00000003084.6
	CFTR	ENST00000699602.1		c.1210-35_1210-34insTGTG		intron	N/A	ENSP00000514471.1
	CFTR	ENST00000426809.5	TSL:5	c.1120-35_1120-34insTGTG		intron	N/A	ENSP00000389119.1

Frequencies

GnomAD3 genomes AF: 0.000927 AC: 133 AN: 143504 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.000458

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000413

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.000216

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000324

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00243 AC: 431 AN: 177682 AF XY: 0.00244

Gnomad AFR exome AF: 0.000438

Gnomad AMR exome AF: 0.00125

Gnomad ASJ exome AF: 0.000156

Gnomad EAS exome AF: 0.0209

Gnomad FIN exome AF: 0.000121

Gnomad NFE exome AF: 0.000320

Gnomad OTH exome AF: 0.000461

GnomAD4 exome AF: 0.000866 AC: 1186 AN: 1370286 Hom.: 0 Cov.: 0 AF XY: 0.000878 AC XY: 598 AN XY: 681206

African (AFR) AF: 0.000663 AC: 21 AN: 31666

American (AMR) AF: 0.000874 AC: 36 AN: 41212

Ashkenazi Jewish (ASJ) AF: 0.0000832 AC: 2 AN: 24032

East Asian (EAS) AF: 0.0115 AC: 425 AN: 36818

South Asian (SAS) AF: 0.00244 AC: 197 AN: 80626

European-Finnish (FIN) AF: 0.0000403 AC: 2 AN: 49642

Middle Eastern (MID) AF: 0.000185 AC: 1 AN: 5420

European-Non Finnish (NFE) AF: 0.000426 AC: 445 AN: 1044472

Other (OTH) AF: 0.00101 AC: 57 AN: 56398

GnomAD4 genome AF: 0.000912 AC: 131 AN: 143604 Hom.: 1 Cov.: 0 AF XY: 0.00100 AC XY: 70 AN XY: 69794

African (AFR) AF: 0.000457 AC: 18 AN: 39392

American (AMR) AF: 0.000412 AC: 6 AN: 14546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3294

East Asian (EAS) AF: 0.0151 AC: 73 AN: 4846

South Asian (SAS) AF: 0.00248 AC: 11 AN: 4444

European-Finnish (FIN) AF: 0.000216 AC: 2 AN: 9248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 254

European-Non Finnish (NFE) AF: 0.000324 AC: 21 AN: 64770

Other (OTH) AF: 0.00 AC: 0 AN: 1996

Alfa AF: 0.000350 Hom.: 240

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cystic fibrosis Benign:2

Dec 18, 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

CFTR-related disorder Benign:1

Oct 22, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

not provided Benign:1

Feb 28, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

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

Splicing

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

Other links and lift over

dbSNP: rs3832534; hg19: chr7-117188660;