rs4730779

Positions:

• chr7-117383481-G-A
• chr7-117383481-G-C
• chr7-117383481-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130768.3(ASZ1):​c.688-371C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,760 control chromosomes in the GnomAD database, including 25,904 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 0.55 (25904 hom., cov: 32)
• Consequence: ASZ1 NM_130768.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASZ1	NM_130768.3	c.688-371C>T		intron_variant		ENST00000284629.7
ASZ1	NM_001301821.2	c.688-371C>T		intron_variant
ASZ1	NM_001301822.2	c.64-371C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASZ1	ENST00000284629.7	c.688-371C>T		intron_variant		1	NM_130768.3	P1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82785 AN: 151640 Hom.: 25837 Cov.: 32

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.546 AC: 82913 AN: 151760 Hom.: 25904 Cov.: 32 AF XY: 0.550 AC XY: 40765 AN XY: 74140

Gnomad4 AFR AF: 0.865

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.501

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.504

Alfa AF: 0.388 Hom.: 1720

Bravo AF: 0.556

Asia WGS AF: 0.543 AC: 1879 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.4
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs4730779; hg19: chr7-117023535;