7-117426924-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_130768.3(ASZ1):c.117G>A(p.Arg39=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00851 in 1,593,834 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0059 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0088 (73 hom.)
• Consequence: ASZ1 NM_130768.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.52

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 7-117426924-C-T is Benign according to our data. Variant chr7-117426924-C-T is described in ClinVar as [Benign]. Clinvar id is 787673.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.53 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASZ1	NM_130768.3	c.117G>A	p.Arg39=	synonymous_variant	2/13	ENST00000284629.7
ASZ1	NM_001301821.2	c.117G>A	p.Arg39=	synonymous_variant	2/13
ASZ1	NM_001301822.2	c.-396G>A		5_prime_UTR_variant	2/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASZ1	ENST00000284629.7	c.117G>A	p.Arg39=	synonymous_variant	2/13	1	NM_130768.3	P1

Frequencies

GnomAD3 genomes AF: 0.00591 AC: 898 AN: 151988 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00541

Gnomad FIN AF: 0.00369

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.00288

GnomAD3 exomes AF: 0.00715 AC: 1671 AN: 233814 Hom.: 10 AF XY: 0.00755 AC XY: 955 AN XY: 126508

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00285

Gnomad ASJ exome AF: 0.00196

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00513

Gnomad FIN exome AF: 0.00314

Gnomad NFE exome AF: 0.0120

Gnomad OTH exome AF: 0.00653

GnomAD4 exome AF: 0.00878 AC: 12661 AN: 1441728 Hom.: 73 Cov.: 30 AF XY: 0.00877 AC XY: 6281 AN XY: 716368

Gnomad4 AFR exome AF: 0.00150

Gnomad4 AMR exome AF: 0.00328

Gnomad4 ASJ exome AF: 0.00249

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00543

Gnomad4 FIN exome AF: 0.00407

Gnomad4 NFE exome AF: 0.0102

Gnomad4 OTH exome AF: 0.00773

GnomAD4 genome AF: 0.00590 AC: 897 AN: 152106 Hom.: 6 Cov.: 32 AF XY: 0.00531 AC XY: 395 AN XY: 74362

Gnomad4 AFR AF: 0.00142

Gnomad4 AMR AF: 0.00464

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00521

Gnomad4 FIN AF: 0.00369

Gnomad4 NFE AF: 0.0101

Gnomad4 OTH AF: 0.00285

Alfa AF: 0.00837 Hom.: 3

Bravo AF: 0.00606

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 15, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.84
Dann	Benign	0.47

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: rs117446983; hg19: chr7-117066978;