rs743572

Variant names:

• chr10-102837395-A-G
• rs743572
• NM_000102.4:c.-34T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-102837395-A-G
• chr10-102837395-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000102.4(CYP17A1):​c.-34T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,408,408 control chromosomes in the GnomAD database, including 106,653 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11779 hom., cov: 32)
  • Exomes 𝑓: 0.39 (94874 hom.)
• Consequence: CYP17A1 NM_000102.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.520
• Publications: 282 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: Orphanet, Labcorp Genetics (formerly Invitae)
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-102837395-A-G is Benign according to our data. Variant chr10-102837395-A-G is described in ClinVar as Benign. ClinVar VariationId is 298630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP17A1	NM_000102.4	MANE Select	c.-34T>C		5_prime_UTR	Exon 1 of 8	NP_000093.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP17A1	ENST00000369887.4	TSL:1 MANE Select	c.-34T>C		5_prime_UTR	Exon 1 of 8	ENSP00000358903.3
	CYP17A1	ENST00000960108.1		c.-34T>C		5_prime_UTR	Exon 1 of 8	ENSP00000630166.1
	CYP17A1	ENST00000960123.1		c.-34T>C		5_prime_UTR	Exon 1 of 8	ENSP00000630182.1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59374 AN: 151974 Hom.: 11760 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.390

GnomAD2 exomes AF: 0.398 AC: 98034 AN: 246120 AF XY: 0.396

Gnomad AFR exome AF: 0.368

Gnomad AMR exome AF: 0.398

Gnomad ASJ exome AF: 0.393

Gnomad EAS exome AF: 0.567

Gnomad FIN exome AF: 0.364

Gnomad NFE exome AF: 0.392

Gnomad OTH exome AF: 0.395

GnomAD4 exome AF: 0.386 AC: 484897 AN: 1256316 Hom.: 94874 Cov.: 18 AF XY: 0.386 AC XY: 245281 AN XY: 635484

African (AFR) AF: 0.369 AC: 10843 AN: 29418

American (AMR) AF: 0.403 AC: 17849 AN: 44344

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 9655 AN: 24866

East Asian (EAS) AF: 0.506 AC: 19595 AN: 38718

South Asian (SAS) AF: 0.367 AC: 30085 AN: 82060

European-Finnish (FIN) AF: 0.367 AC: 19175 AN: 52218

Middle Eastern (MID) AF: 0.397 AC: 2131 AN: 5362

European-Non Finnish (NFE) AF: 0.383 AC: 354541 AN: 925522

Other (OTH) AF: 0.391 AC: 21023 AN: 53808

GnomAD4 genome AF: 0.391 AC: 59442 AN: 152092 Hom.: 11779 Cov.: 32 AF XY: 0.388 AC XY: 28875 AN XY: 74358

African (AFR) AF: 0.370 AC: 15362 AN: 41496

American (AMR) AF: 0.395 AC: 6040 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1382 AN: 3466

East Asian (EAS) AF: 0.561 AC: 2893 AN: 5160

South Asian (SAS) AF: 0.354 AC: 1708 AN: 4830

European-Finnish (FIN) AF: 0.354 AC: 3754 AN: 10590

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27186 AN: 67958

Other (OTH) AF: 0.392 AC: 826 AN: 2108

Alfa AF: 0.392 Hom.: 36074

Bravo AF: 0.395

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Deficiency of steroid 17-alpha-monooxygenase (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.84
DANN	Benign	0.47
PhyloP100		-0.52
PromoterAI		0.0092	Neutral
Mutation Taster		=300/0	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: rs743572; hg19: chr10-104597152; COSMIC: COSV64004809; COSMIC: COSV64004809;