chr7-117610711-A-T

Variant names:

• chr7-117610711-A-T
• rs28517401
• NM_000492.4:c.3139+42A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000492.4(CFTR):​c.3139+42A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,604,986 control chromosomes in the GnomAD database, including 500 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (228 hom., cov: 31)
  • Exomes 𝑓: 0.0095 (272 hom.)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.171
• Publications: 4 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 Gene-Disease associations (from GenCC):

• cystic fibrosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Orphanet
• congenital bilateral absence of vas deferens

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary chronic pancreatitis

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000083622 (HGNC:40145):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-117610711-A-T is Benign according to our data. Variant chr7-117610711-A-T is described in ClinVar as Benign. ClinVar VariationId is 619836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0981 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.3139+42A>T		intron	N/A	NP_000483.3
	CFTR-AS2	NR_199597.1		n.177+5518T>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFTR	ENST00000003084.11	TSL:1 MANE Select	c.3139+42A>T		intron	N/A	ENSP00000003084.6
	CFTR	ENST00000699602.1		c.3139+42A>T		intron	N/A	ENSP00000514471.1
	CFTR	ENST00000426809.5	TSL:5	c.3049+42A>T		intron	N/A	ENSP00000389119.1

Frequencies

GnomAD3 genomes AF: 0.0338 AC: 5151 AN: 152176 Hom.: 221 Cov.: 31

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0123

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0240

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00629

Gnomad OTH AF: 0.0287

GnomAD2 exomes AF: 0.0153 AC: 3777 AN: 247534 AF XY: 0.0145

Gnomad AFR exome AF: 0.100

Gnomad AMR exome AF: 0.00645

Gnomad ASJ exome AF: 0.00370

Gnomad EAS exome AF: 0.00215

Gnomad FIN exome AF: 0.0116

Gnomad NFE exome AF: 0.00660

Gnomad OTH exome AF: 0.00926

GnomAD4 exome AF: 0.00951 AC: 13812 AN: 1452692 Hom.: 272 Cov.: 30 AF XY: 0.00975 AC XY: 7048 AN XY: 722960

African (AFR) AF: 0.105 AC: 3497 AN: 33222

American (AMR) AF: 0.00712 AC: 317 AN: 44534

Ashkenazi Jewish (ASJ) AF: 0.00296 AC: 77 AN: 26000

East Asian (EAS) AF: 0.00292 AC: 115 AN: 39416

South Asian (SAS) AF: 0.0267 AC: 2291 AN: 85744

European-Finnish (FIN) AF: 0.0120 AC: 640 AN: 53124

Middle Eastern (MID) AF: 0.0134 AC: 77 AN: 5738

European-Non Finnish (NFE) AF: 0.00546 AC: 6034 AN: 1104914

Other (OTH) AF: 0.0127 AC: 764 AN: 60000

GnomAD4 genome AF: 0.0340 AC: 5185 AN: 152294 Hom.: 228 Cov.: 31 AF XY: 0.0336 AC XY: 2503 AN XY: 74476

African (AFR) AF: 0.101 AC: 4181 AN: 41552

American (AMR) AF: 0.0123 AC: 188 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3472

East Asian (EAS) AF: 0.00367 AC: 19 AN: 5184

South Asian (SAS) AF: 0.0238 AC: 115 AN: 4828

European-Finnish (FIN) AF: 0.0120 AC: 127 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00629 AC: 428 AN: 68020

Other (OTH) AF: 0.0313 AC: 66 AN: 2112

Alfa AF: 0.00510 Hom.: 4

Bravo AF: 0.0362

Asia WGS AF: 0.0340 AC: 120 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Cystic fibrosis (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.65
PhyloP100		0.17
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: rs28517401; hg19: chr7-117250765;