rs143382119

Variant names:

• chr7-117559732-A-G
• rs143382119
• NM_000492.4:c.1584+77A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000492.4(CFTR):​c.1584+77A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00313 in 980,178 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (70 hom.)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.76
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 7-117559732-A-G is Benign according to our data. Variant chr7-117559732-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 439057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00142 (216/152158) while in subpopulation SAS AF = 0.0425 (205/4828). AF 95% confidence interval is 0.0377. There are 5 homozygotes in GnomAd4. There are 163 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AD,AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFTR	NM_000492.4	MANE Select	c.1584+77A>G		intron	N/A	NP_000483.3
	CFTR-AS1	NR_149084.1		n.221+1001T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFTR	ENST00000003084.11	TSL:1 MANE Select	c.1584+77A>G		intron	N/A	ENSP00000003084.6	P13569-1
	CFTR	ENST00000699596.1		c.*50A>G		3_prime_UTR	Exon 11 of 11	ENSP00000514465.1	A0A8V8TQ89
	CFTR	ENST00000699597.1		c.*219A>G		3_prime_UTR	Exon 11 of 11	ENSP00000514466.1	A0A8V8TNG7

Frequencies

GnomAD3 genomes AF: 0.00142 AC: 216 AN: 152042 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0000968

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0424

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000957

GnomAD4 exome AF: 0.00344 AC: 2849 AN: 828020 Hom.: 70 AF XY: 0.00494 AC XY: 2148 AN XY: 434654

African (AFR) AF: 0.0000480 AC: 1 AN: 20834

American (AMR) AF: 0.0000260 AC: 1 AN: 38392

Ashkenazi Jewish (ASJ) AF: 0.0000455 AC: 1 AN: 21960

East Asian (EAS) AF: 0.00 AC: 0 AN: 35882

South Asian (SAS) AF: 0.0384 AC: 2701 AN: 70380

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43810

Middle Eastern (MID) AF: 0.000957 AC: 3 AN: 3136

European-Non Finnish (NFE) AF: 0.000108 AC: 60 AN: 554112

Other (OTH) AF: 0.00208 AC: 82 AN: 39514

GnomAD4 genome AF: 0.00142 AC: 216 AN: 152158 Hom.: 5 Cov.: 32 AF XY: 0.00219 AC XY: 163 AN XY: 74408

African (AFR) AF: 0.0000965 AC: 4 AN: 41454

American (AMR) AF: 0.0000654 AC: 1 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.0425 AC: 205 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67992

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000416 Hom.: 0

Bravo AF: 0.000268

Asia WGS AF: 0.0120 AC: 40 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.033
DANN	Benign	0.36
PhyloP100		-1.8
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: rs143382119; hg19: chr7-117199786;