dbSNP rs3810171: CYP2S1:c.-177C>T (chr19-41193088-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000880809.1(CYP2S1):c.-177C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0802 in 1,015,514 control chromosomes in the GnomAD database, including 3,836 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 0.10 ( 859 hom., cov: 32)

Exomes 𝑓: 0.077 ( 2977 hom. )

Consequence

CYP2S1
ENST00000880809.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.143

Publications

4 publications found

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:

LOC124904790 (HGNC:):

LOC124904790 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000880809.1. 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.-177C>T		upstream_gene	N/A	NP_085125.1	Q96SQ9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CYP2S1	ENST00000880809.1		c.-177C>T	5_prime_UTR	Exon 1 of 5	ENSP00000550868.1
CYP2S1	ENST00000310054.9	TSL:1 MANE Select	c.-177C>T	upstream_gene	N/A	ENSP00000308032.3	Q96SQ9-1
CYP2S1	ENST00000922089.1		c.-177C>T	upstream_gene	N/A	ENSP00000592148.1

Frequencies

GnomAD3 genomes

AF:

0.100

AC:

15230

AN:

152040

Hom.:

856

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.0900

Gnomad ASJ

AF:

0.125

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.0661

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0805

Gnomad OTH

AF:

0.0979

GnomAD4 exome

AF:

0.0767

AC:

66198

AN:

863356

Hom.:

2977

Cov.:

AF XY:

0.0782

AC XY:

33284

AN XY:

425432

show subpopulations

African (AFR)

AF:

0.115

AC:

1909

AN:

16574

American (AMR)

AF:

0.0853

AC:

1017

AN:

11926

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

1750

AN:

14626

East Asian (EAS)

AF:

0.161

AC:

4130

AN:

25704

South Asian (SAS)

AF:

0.103

AC:

4559

AN:

44232

European-Finnish (FIN)

AF:

0.0739

AC:

2089

AN:

28272

Middle Eastern (MID)

AF:

0.115

AC:

308

AN:

2682

European-Non Finnish (NFE)

AF:

0.0693

AC:

47201

AN:

681258

Other (OTH)

AF:

0.0849

AC:

3235

AN:

38082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

2782

5565

8347

11130

13912

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1590

3180

4770

6360

7950

<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:

0.100

AC:

15253

AN:

152158

Hom.:

859

Cov.:

AF XY:

0.102

AC XY:

7558

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.134

AC:

5569

AN:

41526

American (AMR)

AF:

0.0899

AC:

1376

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

432

AN:

3466

East Asian (EAS)

AF:

0.154

AC:

794

AN:

5148

South Asian (SAS)

AF:

0.120

AC:

577

AN:

4814

European-Finnish (FIN)

AF:

0.0661

AC:

701

AN:

10608

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0805

AC:

5474

AN:

67978

Other (OTH)

AF:

0.0974

AC:

206

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

665

1329

1994

2658

3323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

166

332

498

664

830

<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:

0.0951

Hom.:

111

Bravo

AF:

0.106

Asia WGS

AF:

0.147

AC:

513

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.3

(source)

DANN

Benign

0.95

PhyloP100

0.14

PromoterAI

-0.036

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over