rs6162

Variant names:

• chr10-102837224-G-A
• rs6162
• NM_000102.4:c.138C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-102837224-G-A
• chr10-102837224-G-T

Variant summary

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

The NM_000102.4(CYP17A1):​c.138C>T​(p.His46His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,602,888 control chromosomes in the GnomAD database, including 133,711 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (12664 hom., cov: 32)
  • Exomes 𝑓: 0.41 (121047 hom.)
• Consequence: CYP17A1 NM_000102.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.106
• Publications: 51 publications found

Genes affected

CYP17A1 (HGNC:2593): (cytochrome P450 family 17 subfamily A 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. It has both 17alpha-hydroxylase and 17,20-lyase activities and is a key enzyme in the steroidogenic pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens. Mutations in this gene are associated with isolated steroid-17 alpha-hydroxylase deficiency, 17-alpha-hydroxylase/17,20-lyase deficiency, pseudohermaphroditism, and adrenal hyperplasia. [provided by RefSeq, Jul 2008]

CYP17A1 Gene-Disease associations (from GenCC):

• congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• 46,XY disorder of sex development due to isolated 17,20-lyase deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-102837224-G-A is Benign according to our data. Variant chr10-102837224-G-A is described in ClinVar as Benign. ClinVar VariationId is 298625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.106 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000102.4. 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
	CYP17A1	NM_000102.4	MANE Select	c.138C>T	p.His46His	synonymous	Exon 1 of 8	NP_000093.1	Q1HB44

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP17A1	ENST00000369887.4	TSL:1 MANE Select	c.138C>T	p.His46His	synonymous	Exon 1 of 8	ENSP00000358903.3	P05093
	CYP17A1	ENST00000960108.1		c.138C>T	p.His46His	synonymous	Exon 1 of 8	ENSP00000630166.1
	CYP17A1	ENST00000960123.1		c.138C>T	p.His46His	synonymous	Exon 1 of 8	ENSP00000630182.1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61546 AN: 151954 Hom.: 12650 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.408

GnomAD2 exomes AF: 0.423 AC: 106461 AN: 251466 AF XY: 0.426

Gnomad AFR exome AF: 0.370

Gnomad AMR exome AF: 0.403

Gnomad ASJ exome AF: 0.428

Gnomad EAS exome AF: 0.569

Gnomad FIN exome AF: 0.370

Gnomad NFE exome AF: 0.410

Gnomad OTH exome AF: 0.415

GnomAD4 exome AF: 0.406 AC: 588632 AN: 1450818 Hom.: 121047 Cov.: 30 AF XY: 0.409 AC XY: 295225 AN XY: 722374

African (AFR) AF: 0.370 AC: 12313 AN: 33264

American (AMR) AF: 0.408 AC: 18255 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 11012 AN: 26080

East Asian (EAS) AF: 0.508 AC: 20130 AN: 39632

South Asian (SAS) AF: 0.479 AC: 41213 AN: 86054

European-Finnish (FIN) AF: 0.375 AC: 20016 AN: 53416

Middle Eastern (MID) AF: 0.442 AC: 2540 AN: 5752

European-Non Finnish (NFE) AF: 0.398 AC: 438225 AN: 1101846

Other (OTH) AF: 0.415 AC: 24928 AN: 60052

GnomAD4 genome AF: 0.405 AC: 61602 AN: 152070 Hom.: 12664 Cov.: 32 AF XY: 0.403 AC XY: 29977 AN XY: 74332

African (AFR) AF: 0.373 AC: 15492 AN: 41488

American (AMR) AF: 0.403 AC: 6164 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1525 AN: 3470

East Asian (EAS) AF: 0.563 AC: 2904 AN: 5154

South Asian (SAS) AF: 0.467 AC: 2251 AN: 4822

European-Finnish (FIN) AF: 0.358 AC: 3790 AN: 10574

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.417 AC: 28304 AN: 67952

Other (OTH) AF: 0.410 AC: 868 AN: 2116

Alfa AF: 0.414 Hom.: 19572

Bravo AF: 0.406

Asia WGS AF: 0.469 AC: 1626 AN: 3478

EpiCase AF: 0.407

EpiControl AF: 0.409

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	3	Deficiency of steroid 17-alpha-monooxygenase (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.68
PhyloP100		-0.11
PromoterAI		-0.0084	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs6162; hg19: chr10-104596981; COSMIC: COSV64004807; COSMIC: COSV64004807;