dbSNP rs338583: CYP2S1:c.*31A>G (chr19-41206519-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.22

Variant links:

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]

CYP2S1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CYP2S1	NM_030622.8 link	c.*31A>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000310054.9	NP_085125.1	Q96SQ9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2S1	ENST00000310054.9 link	c.*31A>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_030622.8	ENSP00000308032.3		Q96SQ9-1

Frequencies

GnomAD3 genomes

AF:

0.348

AC:

52871

AN:

151868

Hom.:

10418

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.279

AC XY:

202995

AN XY:

726854

show subpopulations

Gnomad4 AFR exome

AF:

0.564

AC:

18880

AN:

33474

Gnomad4 AMR exome

AF:

0.199

AC:

8921

AN:

44720

Gnomad4 ASJ exome

AF:

0.304

AC:

7944

AN:

26134

Gnomad4 EAS exome

AF:

0.197

AC:

7811

AN:

39700

Gnomad4 SAS exome

AF:

0.243

AC:

20987

AN:

86240

Gnomad4 FIN exome

AF:

0.267

AC:

14234

AN:

53250

Gnomad4 NFE exome

AF:

0.280

AC:

311570

AN:

1111466

Gnomad4 Remaining exome

AF:

0.299

AC:

18062

AN:

60348

Heterozygous variant carriers

17323

34646

51970

69293

86616

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

10364

20728

31092

41456

51820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.348

AC:

52919

AN:

151986

Hom.:

10434

Cov.:

AF XY:

0.344

AC XY:

25564

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.545

AC:

0.545338

AN:

0.545338

Gnomad4 AMR

AF:

0.254

AC:

0.253506

AN:

0.253506

Gnomad4 ASJ

AF:

0.303

AC:

0.302882

AN:

0.302882

Gnomad4 EAS

AF:

0.184

AC:

0.184006

AN:

0.184006

Gnomad4 SAS

AF:

0.228

AC:

0.228121

AN:

0.228121

Gnomad4 FIN

AF:

0.268

AC:

0.268249

AN:

0.268249

Gnomad4 NFE

AF:

0.288

AC:

0.287577

AN:

0.287577

Gnomad4 OTH

AF:

0.332

AC:

0.332384

AN:

0.332384

Heterozygous variant carriers

1669

3337

5006

6674

8343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

500

1000

1500

2000

2500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.81

DANN

Benign

0.42

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over