7-117611845-G-C

Variant names:

• chr7-117611845-G-C
• rs137854873
• NM_000492.4:c.3367+37G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000492.4(CFTR):​c.3367+37G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000226 in 1,325,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: CFTR NM_000492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880
• 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 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:):

CFTR-AS2 (HGNC:40145):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFTR	NM_000492.4	c.3367+37G>C		intron_variant	Intron 20 of 26	ENST00000003084.11	NP_000483.3
CFTR-AS2	NR_199597.1	n.177+4384C>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000003084.11	c.3367+37G>C		intron_variant	Intron 20 of 26	1	NM_000492.4	ENSP00000003084.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000226 AC: 3 AN: 1325100 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 665444

African (AFR) AF: 0.00 AC: 0 AN: 30620

American (AMR) AF: 0.00 AC: 0 AN: 42944

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25208

East Asian (EAS) AF: 0.00 AC: 0 AN: 38636

South Asian (SAS) AF: 0.00 AC: 0 AN: 82424

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49718

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5452

European-Non Finnish (NFE) AF: 0.00000302 AC: 3 AN: 994284

Other (OTH) AF: 0.00 AC: 0 AN: 55814

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.70
DANN	Benign	0.45
PhyloP100		-0.088
PromoterAI		-0.0060	Neutral

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: rs137854873; hg19: chr7-117251899;