chr19-41197865-G-C

Variant names:

• chr19-41197865-G-C
• rs201978576
• NM_030622.8:c.430G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_030622.8(CYP2S1):​c.430G>C​(p.Glu144Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,614,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: CYP2S1 NM_030622.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.160
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.034949124).

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.430G>C	p.Glu144Gln	missense	Exon 3 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.430G>C	p.Glu144Gln	missense	Exon 3 of 9	ENSP00000308032.3	Q96SQ9-1
	CYP2S1	ENST00000922089.1		c.430G>C	p.Glu144Gln	missense	Exon 3 of 9	ENSP00000592148.1
	CYP2S1	ENST00000922088.1		c.430G>C	p.Glu144Gln	missense	Exon 3 of 8	ENSP00000592147.1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152222 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000915 AC: 23 AN: 251286 AF XY: 0.000103

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000816

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000390 AC: 57 AN: 1461814 Hom.: 0 Cov.: 34 AF XY: 0.0000481 AC XY: 35 AN XY: 727202

African (AFR) AF: 0.0000597 AC: 2 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000277 AC: 11 AN: 39700

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1112006

Other (OTH) AF: 0.000364 AC: 22 AN: 60390

GnomAD4 genome AF: 0.0000853 AC: 13 AN: 152340 Hom.: 0 Cov.: 31 AF XY: 0.0000806 AC XY: 6 AN XY: 74486

African (AFR) AF: 0.0000481 AC: 2 AN: 41588

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5178

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000659 AC: 8

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0041	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.13	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.16
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.22
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.073	T
Polyphen		0.99	D
Vest4		0.34
MVP		0.54
MPC		0.66
ClinPred		0.095	T
GERP RS		4.9
Varity_R		0.33
gMVP		0.50
Mutation Taster		=100/0	polymorphism

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: rs201978576; hg19: chr19-41703770;