12-121024336-G-C

Position:

• chr12-121024336-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003733.4(OASL):​c.900-199C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,040 control chromosomes in the GnomAD database, including 21,059 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 0.51 (21059 hom., cov: 32)
• Consequence: OASL NM_003733.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02

Genes affected

OASL (HGNC:8090): (2'-5'-oligoadenylate synthetase like) Enables DNA binding activity and double-stranded RNA binding activity. Involved in several processes, including interleukin-27-mediated signaling pathway; negative regulation of viral genome replication; and positive regulation of RIG-I signaling pathway. Located in cytosol; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OASL	NM_003733.4	c.900-199C>G		intron_variant		ENST00000257570.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OASL	ENST00000257570.10	c.900-199C>G		intron_variant		1	NM_003733.4	P1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77768 AN: 151922 Hom.: 21038 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.644

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.512 AC: 77824 AN: 152040 Hom.: 21059 Cov.: 32 AF XY: 0.517 AC XY: 38467 AN XY: 74334

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.673

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.735

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.553

Alfa AF: 0.501 Hom.: 2418

Bravo AF: 0.519

Asia WGS AF: 0.668 AC: 2320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.7
DANN	Benign	0.44

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: rs2259883; hg19: chr12-121462139;