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GeneBe

19-41197858-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_030622.8(CYP2S1):c.423G>A(p.Gly141=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,614,134 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 51 hom., cov: 31)
Exomes 𝑓: 0.0013 ( 40 hom. )

Consequence

CYP2S1
NM_030622.8 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.157
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-41197858-G-A is Benign according to our data. Variant chr19-41197858-G-A is described in ClinVar as [Benign]. Clinvar id is 788469.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.157 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.014 (2130/152312) while in subpopulation AFR AF= 0.0485 (2017/41566). AF 95% confidence interval is 0.0468. There are 51 homozygotes in gnomad4. There are 1025 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 51 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CYP2S1NM_030622.8 linkuse as main transcriptc.423G>A p.Gly141= synonymous_variant 3/9 ENST00000310054.9
CYP2S1XM_047438711.1 linkuse as main transcriptc.423G>A p.Gly141= synonymous_variant 3/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CYP2S1ENST00000310054.9 linkuse as main transcriptc.423G>A p.Gly141= synonymous_variant 3/91 NM_030622.8 P1Q96SQ9-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0140
AC:
2131
AN:
152194
Hom.:
51
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0487
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00569
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00765
GnomAD3 exomes
AF:
0.00365
AC:
918
AN:
251304
Hom.:
20
AF XY:
0.00272
AC XY:
370
AN XY:
135818
show subpopulations
Gnomad AFR exome
AF:
0.0489
Gnomad AMR exome
AF:
0.00272
Gnomad ASJ exome
AF:
0.000298
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000967
Gnomad OTH exome
AF:
0.00228
GnomAD4 exome
AF:
0.00133
AC:
1948
AN:
1461822
Hom.:
40
Cov.:
35
AF XY:
0.00115
AC XY:
837
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.0464
Gnomad4 AMR exome
AF:
0.00295
Gnomad4 ASJ exome
AF:
0.000268
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000812
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000468
Gnomad4 OTH exome
AF:
0.00308
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0140
AC:
2130
AN:
152312
Hom.:
51
Cov.:
31
AF XY:
0.0138
AC XY:
1025
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.0485
Gnomad4 AMR
AF:
0.00568
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00757
Alfa
AF:
0.00360
Hom.:
12
Bravo
AF:
0.0160
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 28, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.43
Cadd
Benign
4.0
Dann
Benign
0.68

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.

Other links and lift over

dbSNP: rs16975056; hg19: chr19-41703763; API