9-116687467-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001365068.1(ASTN2):c.2807-35674G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0838 in 143,324 control chromosomes in the GnomAD database, including 526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.084 (487 hom., cov: 21)
  • Exomes 𝑓: 0.080 (39 hom.)
• Consequence: ASTN2 NM_001365068.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.68

Genes affected

ASTN2 (HGNC:17021): (astrotactin 2) This gene encodes a protein that is expressed in the brain and may function in neuronal migration, based on functional studies of the related astrotactin 1 gene in human and mouse. A deletion at this locus has been associated with schizophrenia. Multiple transcript variants encoding different proteins have been found for this locus. [provided by RefSeq, May 2010]

TRIM32 (HGNC:16380): (tripartite motif containing 32) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to cytoplasmic bodies. The protein has also been localized to the nucleus, where it interacts with the activation domain of the HIV-1 Tat protein. The Tat protein activates transcription of HIV-1 genes. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-116687467-C-T is Benign according to our data. Variant chr9-116687467-C-T is described in ClinVar as [Benign]. Clinvar id is 1220919.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASTN2	NM_001365068.1	c.2807-35674G>A		intron_variant		ENST00000313400.9
TRIM32	NM_012210.4	c.-82+86C>T		intron_variant		ENST00000450136.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASTN2	ENST00000313400.9	c.2807-35674G>A		intron_variant		5	NM_001365068.1	A2
TRIM32	ENST00000450136.2	c.-82+86C>T		intron_variant		1	NM_012210.4	P1

Frequencies

GnomAD3 genomes AF: 0.0841 AC: 11173 AN: 132792 Hom.: 485 Cov.: 21

Gnomad AFR AF: 0.0497

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0865

Gnomad ASJ AF: 0.0609

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.0731

Gnomad NFE AF: 0.0891

Gnomad OTH AF: 0.0797

GnomAD4 exome AF: 0.0805 AC: 841 AN: 10448 Hom.: 39 AF XY: 0.0799 AC XY: 403 AN XY: 5046

Gnomad4 AFR exome AF: 0.0529

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0577

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.0885

Gnomad4 NFE exome AF: 0.0804

Gnomad4 OTH exome AF: 0.101

GnomAD4 genome AF: 0.0841 AC: 11174 AN: 132876 Hom.: 487 Cov.: 21 AF XY: 0.0871 AC XY: 5507 AN XY: 63244

Gnomad4 AFR AF: 0.0498

Gnomad4 AMR AF: 0.0864

Gnomad4 ASJ AF: 0.0609

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.0891

Gnomad4 OTH AF: 0.0798

Alfa AF: 0.0369 Hom.: 24

Bravo AF: 0.0768

Asia WGS AF: 0.140 AC: 485 AN: 3468

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

GeneDx

Apr 11, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.17
Dann	Benign	0.91

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: rs112643631; hg19: chr9-119449746; COSMIC: COSV56006515; COSMIC: COSV56006515;