19-41193319-C-T

Variant names:

• chr19-41193319-C-T
• rs373031805
• NM_030622.8:c.55C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_030622.8(CYP2S1):​c.55C>T​(p.Leu19Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,389,454 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CYP2S1 NM_030622.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 0 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=0.252 with no splicing effect.

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.55C>T	p.Leu19Leu	synonymous	Exon 1 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.55C>T	p.Leu19Leu	synonymous	Exon 1 of 9	ENSP00000308032.3	Q96SQ9-1
	CYP2S1	ENST00000922089.1		c.55C>T	p.Leu19Leu	synonymous	Exon 1 of 9	ENSP00000592148.1
	CYP2S1	ENST00000922088.1		c.55C>T	p.Leu19Leu	synonymous	Exon 1 of 8	ENSP00000592147.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1389454 Hom.: 0 Cov.: 31 AF XY: 0.00000146 AC XY: 1 AN XY: 685146

African (AFR) AF: 0.00 AC: 0 AN: 30640

American (AMR) AF: 0.00 AC: 0 AN: 35178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24850

East Asian (EAS) AF: 0.00 AC: 0 AN: 35280

South Asian (SAS) AF: 0.00 AC: 0 AN: 78952

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4158

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1076054

Other (OTH) AF: 0.00 AC: 0 AN: 57460

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.96
PhyloP100		0.25
PromoterAI		-0.045	Neutral

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: rs373031805; hg19: chr19-41699224;