chr7-117427768-T-G

Variant names:

• chr7-117427768-T-G
• rs7808424
• ENST00000673785.1:c.-490-37979T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000673785.1(CFTR):​c.-490-37979T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,248 control chromosomes in the GnomAD database, including 1,534 homozygotes. 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: 𝑓 0.11 (1534 hom., cov: 32)
• Consequence: CFTR ENST00000673785.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 19 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]

ASZ1 (HGNC:1350): (ankyrin repeat, SAM and basic leucine zipper domain containing 1) Predicted to be involved in gamete generation and piRNA metabolic process. Predicted to be located in cytoplasm. Predicted to be active in pi-body. [provided by Alliance of Genome Resources, Apr 2022]

ASZ1 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFTR	ENST00000673785.1	c.-490-37979T>G		intron_variant	Intron 2 of 12			ENSP00000501235.1
ASZ1	ENST00000428663.1	c.-55+302A>C		intron_variant	Intron 1 of 2	5		ENSP00000402919.1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17047 AN: 152130 Hom.: 1527 Cov.: 32

Gnomad AFR AF: 0.0721

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0831

Gnomad OTH AF: 0.102

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.112 AC: 17068 AN: 152248 Hom.: 1534 Cov.: 32 AF XY: 0.119 AC XY: 8890 AN XY: 74420

African (AFR) AF: 0.0721 AC: 2996 AN: 41578

American (AMR) AF: 0.209 AC: 3193 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0536 AC: 186 AN: 3470

East Asian (EAS) AF: 0.448 AC: 2307 AN: 5146

South Asian (SAS) AF: 0.293 AC: 1410 AN: 4814

European-Finnish (FIN) AF: 0.101 AC: 1070 AN: 10616

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0831 AC: 5651 AN: 68002

Other (OTH) AF: 0.102 AC: 216 AN: 2114

Alfa AF: 0.104 Hom.: 4044

Bravo AF: 0.119

Asia WGS AF: 0.372 AC: 1295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.6
DANN	Benign	0.75
PhyloP100		-0.037
PromoterAI		0.018	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7808424; hg19: chr7-117067822;