rs2069709

Positions:

• chr12-68159923-C-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP5 BP4 BS1_Supporting BS2

The variant allele was found at a frequency of 0.00692 in 152,262 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: 𝑓 0.0069 (11 hom., cov: 31)
• Consequence: intergenic_region
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.404

Genes affected

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PP5: Variant 12-68159923-C-A is Pathogenic according to our data. Variant chr12-68159923-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 14724.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34). . Strength limited to SUPPORTING due to the PP5.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00692 (1053/152262) while in subpopulation AFR AF= 0.0241 (1000/41534). AF 95% confidence interval is 0.0228. There are 11 homozygotes in gnomad4. There are 495 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.68159923C>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNG-AS1	ENST00000536914.1	n.337-74606C>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00691 AC: 1051 AN: 152144 Hom.: 12 Cov.: 31

Gnomad AFR AF: 0.0241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00384

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

GnomAD4 genome AF: 0.00692 AC: 1053 AN: 152262 Hom.: 11 Cov.: 31 AF XY: 0.00665 AC XY: 495 AN XY: 74462

Gnomad4 AFR AF: 0.0241

Gnomad4 AMR AF: 0.00235

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00380

Alfa AF: 0.00906 Hom.: 1

Bravo AF: 0.00790

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Acquired immunodeficiency syndrome, rapid progression to Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 15, 2003

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	16
DANN	Benign	0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2069709; hg19: chr12-68553703;