chr7-117548606-A-ATGTGTGTG

Variant names:

• chr7-117548606-A-ATGTGTGTG
• rs3832534
• NM_000492.4:c.1210-19_1210-12dupGTGTGTGT

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_1210-12dupGTGTGTGT 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 0.000035 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• 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: Likely_benign. The variant received -1 ACMG points.

• BP6: Variant 7-117548606-A-ATGTGTGTG is Benign according to our data. Variant chr7-117548606-A-ATGTGTGTG is described in ClinVar as Likely_benign. ClinVar VariationId is 3030509.Status of the report is no_assertion_criteria_provided, 0 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.1210-19_1210-12dupGTGTGTGT		intron	N/A	NP_000483.3
	CFTR-AS1	NR_149084.1		n.222-6075_222-6068dupCACACACA		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_1210-34insTGTGTGTG		intron	N/A	ENSP00000003084.6
	CFTR	ENST00000699602.1		c.1210-35_1210-34insTGTGTGTG		intron	N/A	ENSP00000514471.1
	CFTR	ENST00000426809.5	TSL:5	c.1120-35_1120-34insTGTGTGTG		intron	N/A	ENSP00000389119.1

Frequencies

GnomAD3 genomes AF: 0.0000348 AC: 5 AN: 143508 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

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: 0.0000772

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000507 AC: 9 AN: 177682 AF XY: 0.0000418

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000146

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000667

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000146 AC: 20 AN: 1370526 Hom.: 0 Cov.: 0 AF XY: 0.0000147 AC XY: 10 AN XY: 681288

African (AFR) AF: 0.00 AC: 0 AN: 31670

American (AMR) AF: 0.000121 AC: 5 AN: 41254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24034

East Asian (EAS) AF: 0.00 AC: 0 AN: 36852

South Asian (SAS) AF: 0.00 AC: 0 AN: 80644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49644

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5422

European-Non Finnish (NFE) AF: 0.0000144 AC: 15 AN: 1044598

Other (OTH) AF: 0.00 AC: 0 AN: 56408

GnomAD4 genome AF: 0.0000348 AC: 5 AN: 143508 Hom.: 0 Cov.: 0 AF XY: 0.0000287 AC XY: 2 AN XY: 69684

African (AFR) AF: 0.00 AC: 0 AN: 39280

American (AMR) AF: 0.00 AC: 0 AN: 14530

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4860

South Asian (SAS) AF: 0.00 AC: 0 AN: 4456

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 276

European-Non Finnish (NFE) AF: 0.0000772 AC: 5 AN: 64778

Other (OTH) AF: 0.00 AC: 0 AN: 1972

Alfa AF: 0.0000500 Hom.: 240

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CFTR-related disorder Benign:1

Nov 23, 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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.065
La Branchor		0.64
BranchPoint Hunter		2.0

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;