rs4730779

Variant names:

• chr7-117383481-G-A
• rs4730779
• NM_130768.3:c.688-371C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

CFTR Gene-Disease associations (from GenCC):

• cystic fibrosis

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

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 (AFR) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130768.3. 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
	ASZ1	NM_130768.3	MANE Select	c.688-371C>T		intron	N/A	NP_570124.1	Q8WWH4-1
	ASZ1	NM_001301821.2		c.688-371C>T		intron	N/A	NP_001288750.1	Q8WWH4-2
	ASZ1	NM_001301822.2		c.64-371C>T		intron	N/A	NP_001288751.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASZ1	ENST00000284629.7	TSL:1 MANE Select	c.688-371C>T		intron	N/A	ENSP00000284629.2	Q8WWH4-1
	ASZ1	ENST00000450714.2	TSL:1	n.*129-371C>T		intron	N/A	ENSP00000389791.2	F8WDQ2
	CFTR	ENST00000673785.1		c.-490-82266G>A		intron	N/A	ENSP00000501235.1	A0A669KBE8

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

African (AFR) AF: 0.865 AC: 35929 AN: 41516

American (AMR) AF: 0.512 AC: 7799 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 939 AN: 3468

East Asian (EAS) AF: 0.461 AC: 2378 AN: 5156

South Asian (SAS) AF: 0.501 AC: 2417 AN: 4822

European-Finnish (FIN) AF: 0.532 AC: 5604 AN: 10526

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26429 AN: 67748

Other (OTH) AF: 0.504 AC: 1058 AN: 2100

Alfa AF: 0.442 Hom.: 5006

Bravo AF: 0.556

Asia WGS AF: 0.543 AC: 1879 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.4
DANN	Benign	0.56
PhyloP100		0.39
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: rs4730779; hg19: chr7-117023535;