chr7-117548606-ATGTG-A

Variant names:

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

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_1210-12delGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000822 in 1,497,250 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00088 (1 hom.)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• 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 -8 ACMG points.

• BP6: Variant 7-117548606-ATGTG-A is Benign according to our data. Variant chr7-117548606-ATGTG-A is described in ClinVar as Benign. ClinVar VariationId is 439490.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_1210-12delGTGT		intron	N/A	NP_000483.3
	CFTR-AS1	NR_149084.1		n.222-6071_222-6068delCACA		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_1210-31delTGTG		intron	N/A	ENSP00000003084.6
	CFTR	ENST00000699602.1		c.1210-34_1210-31delTGTG		intron	N/A	ENSP00000514471.1
	CFTR	ENST00000426809.5	TSL:5	c.1120-34_1120-31delTGTG		intron	N/A	ENSP00000389119.1

Frequencies

GnomAD3 genomes AF: 0.000286 AC: 41 AN: 143484 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000509

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00110

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000108

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000618

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00135 AC: 239 AN: 177682 AF XY: 0.00128

Gnomad AFR exome AF: 0.00569

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.000312

Gnomad EAS exome AF: 0.0000694

Gnomad FIN exome AF: 0.00115

Gnomad NFE exome AF: 0.00144

Gnomad OTH exome AF: 0.00138

GnomAD4 exome AF: 0.000878 AC: 1189 AN: 1353668 Hom.: 1 AF XY: 0.000944 AC XY: 635 AN XY: 672934

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00586 AC: 172 AN: 29342

American (AMR) AF: 0.00149 AC: 61 AN: 40934

Ashkenazi Jewish (ASJ) AF: 0.000126 AC: 3 AN: 23852

East Asian (EAS) AF: 0.0000272 AC: 1 AN: 36798

South Asian (SAS) AF: 0.000363 AC: 29 AN: 79980

European-Finnish (FIN) AF: 0.00201 AC: 98 AN: 48658

Middle Eastern (MID) AF: 0.000933 AC: 5 AN: 5360

European-Non Finnish (NFE) AF: 0.000719 AC: 743 AN: 1033056

Other (OTH) AF: 0.00138 AC: 77 AN: 55688

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000286 AC: 41 AN: 143582 Hom.: 0 Cov.: 0 AF XY: 0.000315 AC XY: 22 AN XY: 69784

African (AFR) AF: 0.000508 AC: 20 AN: 39384

American (AMR) AF: 0.00110 AC: 16 AN: 14548

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4848

South Asian (SAS) AF: 0.00 AC: 0 AN: 4444

European-Finnish (FIN) AF: 0.000108 AC: 1 AN: 9238

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

European-Non Finnish (NFE) AF: 0.0000618 AC: 4 AN: 64764

Other (OTH) AF: 0.00 AC: 0 AN: 1994

Alfa AF: 0.00255 Hom.: 240

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cystic fibrosis Benign:2

Nov 19, 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

Mar 04, 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).

not provided Benign:1

Oct 22, 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		0.075
La Branchor		0.64
BranchPoint Hunter		2.0
Mutation Taster		=100/0	polymorphism

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;