chr12-121038620-A-G

Variant names:

• chr12-121038620-A-G
• rs10774580
• NM_003733.4:c.198+154T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003733.4(OASL):​c.198+154T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,056 control chromosomes in the GnomAD database, including 24,221 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 0.55 (24221 hom., cov: 32)
• Consequence: OASL NM_003733.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.769
• Publications: 21 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.685 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.198+154T>C		intron	N/A	NP_003724.1
	OASL	NM_001261825.2		c.198+154T>C		intron	N/A	NP_001248754.1
	OASL	NM_001395419.1		c.198+154T>C		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.198+154T>C		intron	N/A	ENSP00000257570.4
	OASL	ENST00000620239.6	TSL:1	c.198+154T>C		intron	N/A	ENSP00000479512.1
	OASL	ENST00000339275.10	TSL:1	c.198+154T>C		intron	N/A	ENSP00000341125.5

Frequencies

GnomAD3 genomes AF: 0.553 AC: 84067 AN: 151938 Hom.: 24215 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.582

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

GnomAD4 genome AF: 0.553 AC: 84103 AN: 152056 Hom.: 24221 Cov.: 32 AF XY: 0.553 AC XY: 41085 AN XY: 74320

African (AFR) AF: 0.382 AC: 15855 AN: 41476

American (AMR) AF: 0.660 AC: 10063 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 2141 AN: 3472

East Asian (EAS) AF: 0.613 AC: 3168 AN: 5164

South Asian (SAS) AF: 0.704 AC: 3395 AN: 4820

European-Finnish (FIN) AF: 0.541 AC: 5720 AN: 10570

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.616 AC: 41844 AN: 67978

Other (OTH) AF: 0.585 AC: 1237 AN: 2114

Alfa AF: 0.589 Hom.: 56526

Bravo AF: 0.550

Asia WGS AF: 0.621 AC: 2159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.48
PhyloP100		-0.77
PromoterAI		0.017	Neutral
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: rs10774580; hg19: chr12-121476423; COSMIC: COSV57479036;