chr12-121024336-G-C

Variant names:

• chr12-121024336-G-C
• rs2259883
• NM_003733.4:c.900-199C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003733.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OASL	NM_003733.4	MANE Select	c.900-199C>G		intron	N/A	NP_003724.1
	OASL	NM_001261825.2		c.658-3278C>G		intron	N/A	NP_001248754.1
	OASL	NM_001395419.1		c.900-199C>G		intron	N/A	NP_001382348.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OASL	ENST00000257570.10	TSL:1 MANE Select	c.900-199C>G		intron	N/A	ENSP00000257570.4
	OASL	ENST00000620239.6	TSL:1	c.658-3278C>G		intron	N/A	ENSP00000479512.1
	OASL	ENST00000339275.10	TSL:1	c.658-199C>G		intron	N/A	ENSP00000341125.5

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

African (AFR) AF: 0.349 AC: 14454 AN: 41468

American (AMR) AF: 0.673 AC: 10278 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 2094 AN: 3464

East Asian (EAS) AF: 0.735 AC: 3799 AN: 5166

South Asian (SAS) AF: 0.582 AC: 2808 AN: 4824

European-Finnish (FIN) AF: 0.518 AC: 5479 AN: 10568

Middle Eastern (MID) AF: 0.634 AC: 184 AN: 290

European-Non Finnish (NFE) AF: 0.544 AC: 36983 AN: 67960

Other (OTH) AF: 0.553 AC: 1167 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.7
DANN	Benign	0.44
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2259883; hg19: chr12-121462139;