rs2017319

Variant names:

• chr10-94988878-C-T
• rs2017319
• NM_000771.4:c.1323C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-94988878-C-T
• chr10-94988878-C-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000771.4(CYP2C9):​c.1323C>T​(p.Ala441Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00592 in 1,613,836 control chromosomes in the GnomAD database, including 414 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (242 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (172 hom.)
• Consequence: CYP2C9 NM_000771.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0580
• Publications: 15 publications found

Genes affected

CYP2C9 (HGNC:2623): (cytochrome P450 family 2 subfamily C member 9) 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 and its expression is induced by rifampin. The enzyme is known to metabolize many xenobiotics, including phenytoin, tolbutamide, ibuprofen and S-warfarin. Studies identifying individuals who are poor metabolizers of phenytoin and tolbutamide suggest that this gene is polymorphic. The gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 10-94988878-C-T is Benign according to our data. Variant chr10-94988878-C-T is described in ClinVar as Benign. ClinVar VariationId is 776530.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.058 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000771.4. 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
	CYP2C9	NM_000771.4	MANE Select	c.1323C>T	p.Ala441Ala	synonymous	Exon 9 of 9	NP_000762.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C9	ENST00000260682.8	TSL:1 MANE Select	c.1323C>T	p.Ala441Ala	synonymous	Exon 9 of 9	ENSP00000260682.6	P11712-1
	CYP2C9	ENST00000880948.1		c.1344C>T	p.Ala448Ala	synonymous	Exon 9 of 9	ENSP00000551007.1
	CYP2C9	ENST00000880956.1		c.1344C>T	p.Ala448Ala	synonymous	Exon 9 of 9	ENSP00000551015.1

Frequencies

GnomAD3 genomes AF: 0.0305 AC: 4641 AN: 152104 Hom.: 242 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0161

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.0220

GnomAD2 exomes AF: 0.00847 AC: 2130 AN: 251376 AF XY: 0.00654

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.00692

Gnomad ASJ exome AF: 0.00109

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000774

Gnomad OTH exome AF: 0.00652

GnomAD4 exome AF: 0.00337 AC: 4921 AN: 1461614 Hom.: 172 Cov.: 32 AF XY: 0.00294 AC XY: 2136 AN XY: 727124

African (AFR) AF: 0.100 AC: 3361 AN: 33448

American (AMR) AF: 0.00830 AC: 371 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00122 AC: 32 AN: 26128

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86252

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53418

Middle Eastern (MID) AF: 0.0117 AC: 67 AN: 5728

European-Non Finnish (NFE) AF: 0.000550 AC: 611 AN: 1111858

Other (OTH) AF: 0.00767 AC: 463 AN: 60384

GnomAD4 genome AF: 0.0305 AC: 4638 AN: 152222 Hom.: 242 Cov.: 32 AF XY: 0.0291 AC XY: 2163 AN XY: 74436

African (AFR) AF: 0.103 AC: 4291 AN: 41508

American (AMR) AF: 0.0161 AC: 246 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10610

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.000632 AC: 43 AN: 68026

Other (OTH) AF: 0.0218 AC: 46 AN: 2110

Alfa AF: 0.00963 Hom.: 238

Bravo AF: 0.0354

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	9.1
DANN	Benign	0.35
PhyloP100		-0.058
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2017319; hg19: chr10-96748635;