rs338583

Positions:

• chr19-41206519-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. Variant has been reported in Lovd as Likely benign (no stars).

• 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

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 19-41206519-A-G is Benign according to our data. Variant chr19-41206519-A-G is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2S1	NM_030622.8	c.*31A>G		3_prime_UTR_variant	9/9	ENST00000310054.9	NP_085125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2S1	ENST00000310054.9	c.*31A>G		3_prime_UTR_variant	9/9	1	NM_030622.8	ENSP00000308032	P1
CYP2S1	ENST00000593890.1	c.*240A>G		3_prime_UTR_variant	3/3	3		ENSP00000469850
CYP2S1	ENST00000593545.5	c.*557A>G		3_prime_UTR_variant, NMD_transcript_variant	6/6	2		ENSP00000472555

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

GnomAD3 exomes AF: 0.275 AC: 69087 AN: 250974 Hom.: 10581 AF XY: 0.273 AC XY: 37091 AN XY: 135652

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 SAS exome AF: 0.239

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

Gnomad4 AFR exome AF: 0.564

Gnomad4 AMR exome AF: 0.199

Gnomad4 ASJ exome AF: 0.304

Gnomad4 EAS exome AF: 0.197

Gnomad4 SAS exome AF: 0.243

Gnomad4 FIN exome AF: 0.267

Gnomad4 NFE exome AF: 0.280

Gnomad4 OTH exome AF: 0.299

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

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.332

Alfa AF: 0.300 Hom.: 6798

Bravo AF: 0.355

Asia WGS AF: 0.217 AC: 755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.81
DANN	Benign	0.42

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: rs338583; hg19: chr19-41712424; COSMIC: COSV59505063; COSMIC: COSV59505063;