rs338583

Variant names:

• chr19-41206519-A-G
• rs338583
• NM_030622.8:c.*31A>G

Variant summary

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

The NM_030622.8(CYP2S1):​c.*31A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,613,084 control chromosomes in the GnomAD database, including 70,125 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 0.35 (10434 hom., cov: 31)
  • Exomes 𝑓: 0.28 (59691 hom.)
• Consequence: CYP2S1 NM_030622.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 21 publications found

Genes affected

CYP2S1 (HGNC:15654): (cytochrome P450 family 2 subfamily S member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum. In rodents, the homologous protein has been shown to metabolize certain carcinogens; however, the specific function of the human protein has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030622.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2S1	NM_030622.8	MANE Select	c.*31A>G		3_prime_UTR	Exon 9 of 9	NP_085125.1	Q96SQ9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2S1	ENST00000310054.9	TSL:1 MANE Select	c.*31A>G		3_prime_UTR	Exon 9 of 9	ENSP00000308032.3	Q96SQ9-1
	CYP2S1	ENST00000922089.1		c.*31A>G		3_prime_UTR	Exon 9 of 9	ENSP00000592148.1
	CYP2S1	ENST00000922088.1		c.*31A>G		3_prime_UTR	Exon 8 of 8	ENSP00000592147.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52871 AN: 151868 Hom.: 10418 Cov.: 31

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.335

GnomAD2 exomes AF: 0.275 AC: 69087 AN: 250974 AF XY: 0.273

Gnomad AFR exome AF: 0.554

Gnomad AMR exome AF: 0.189

Gnomad ASJ exome AF: 0.299

Gnomad EAS exome AF: 0.184

Gnomad FIN exome AF: 0.264

Gnomad NFE exome AF: 0.285

Gnomad OTH exome AF: 0.292

GnomAD4 exome AF: 0.281 AC: 410301 AN: 1461098 Hom.: 59691 Cov.: 35 AF XY: 0.279 AC XY: 202995 AN XY: 726854

African (AFR) AF: 0.564 AC: 18880 AN: 33474

American (AMR) AF: 0.199 AC: 8921 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 7944 AN: 26134

East Asian (EAS) AF: 0.197 AC: 7811 AN: 39700

South Asian (SAS) AF: 0.243 AC: 20987 AN: 86240

European-Finnish (FIN) AF: 0.267 AC: 14234 AN: 53250

Middle Eastern (MID) AF: 0.328 AC: 1892 AN: 5766

European-Non Finnish (NFE) AF: 0.280 AC: 311570 AN: 1111466

Other (OTH) AF: 0.299 AC: 18062 AN: 60348

GnomAD4 genome AF: 0.348 AC: 52919 AN: 151986 Hom.: 10434 Cov.: 31 AF XY: 0.344 AC XY: 25564 AN XY: 74282

African (AFR) AF: 0.545 AC: 22601 AN: 41444

American (AMR) AF: 0.254 AC: 3868 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1051 AN: 3470

East Asian (EAS) AF: 0.184 AC: 948 AN: 5152

South Asian (SAS) AF: 0.228 AC: 1100 AN: 4822

European-Finnish (FIN) AF: 0.268 AC: 2837 AN: 10576

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19542 AN: 67954

Other (OTH) AF: 0.332 AC: 700 AN: 2106

Alfa AF: 0.315 Hom.: 12846

Bravo AF: 0.355

Asia WGS AF: 0.217 AC: 755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.81
DANN	Benign	0.42
PhyloP100		-1.2
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: rs338583; hg19: chr19-41712424; COSMIC: COSV59505063; COSMIC: COSV59505063;