1-159062696-GT-G

Position:

• chr1-159062696-GT-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4 BP6_Moderate BS2

The NM_004833.3(AIM2):​c.1027del​(p.Thr343HisfsTer14) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00443 in 1,390,226 control chromosomes in the GnomAD database, including 15 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0046 (12 hom.)
• Consequence: AIM2 NM_004833.3 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0140

Genes affected

AIM2 (HGNC:357): (absent in melanoma 2) AIM2 is a member of the IFI20X /IFI16 family. It plays a putative role in tumorigenic reversion and may control cell proliferation. Interferon-gamma induces expression of AIM2. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM4: Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 439 codons.
• BP6: Variant 1-159062696-GT-G is Benign according to our data. Variant chr1-159062696-GT-G is described in ClinVar as [Benign]. Clinvar id is 3041346.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AIM2	NM_004833.3	c.1027del	p.Thr343HisfsTer14	frameshift_variant	6/6	ENST00000368130.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AIM2	ENST00000368130.9	c.1027del	p.Thr343HisfsTer14	frameshift_variant	6/6	1	NM_004833.3	P1
AIM2	ENST00000411768.2	c.1027del	p.Thr343HisfsTer14	frameshift_variant	9/9	5		P1
AIM2	ENST00000695580.1	c.1027del	p.Thr343HisfsTer14	frameshift_variant	7/7			P1
AIM2	ENST00000695579.1	c.616del	p.Thr206HisfsTer14	frameshift_variant	5/5

Frequencies

GnomAD3 genomes AF: 0.00290 AC: 428 AN: 147422 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000919

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00298

Gnomad ASJ AF: 0.00765

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000644

Gnomad FIN AF: 0.00230

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.00435

Gnomad OTH AF: 0.00297

GnomAD4 exome AF: 0.00461 AC: 5727 AN: 1242724 Hom.: 12 Cov.: 31 AF XY: 0.00454 AC XY: 2813 AN XY: 619522

Gnomad4 AFR exome AF: 0.00196

Gnomad4 AMR exome AF: 0.00481

Gnomad4 ASJ exome AF: 0.00564

Gnomad4 EAS exome AF: 0.000361

Gnomad4 SAS exome AF: 0.00221

Gnomad4 FIN exome AF: 0.00391

Gnomad4 NFE exome AF: 0.00501

Gnomad4 OTH exome AF: 0.00442

GnomAD4 genome AF: 0.00291 AC: 429 AN: 147502 Hom.: 3 Cov.: 32 AF XY: 0.00284 AC XY: 204 AN XY: 71742

Gnomad4 AFR AF: 0.000941

Gnomad4 AMR AF: 0.00298

Gnomad4 ASJ AF: 0.00765

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000646

Gnomad4 FIN AF: 0.00230

Gnomad4 NFE AF: 0.00435

Gnomad4 OTH AF: 0.00294

Alfa AF: 0.0101 Hom.: 0

Bravo AF: 0.00286

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

AIM2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 12, 2021

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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: rs531843702; hg19: chr1-159032486;