rs1065779

chr15-51212614-A-Cchr15-51212614-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000103.4(CYP19A1):c.1022-53T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 1,183,222 control chromosomes in the GnomAD database, including 144,940 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (15260 hom., cov: 32)
  • Exomes 𝑓: 0.50 (129680 hom.)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.802

Genes affected

CYP19A1 (HGNC:2594): (cytochrome P450 family 19 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 and catalyzes the last steps of estrogen biosynthesis. Mutations in this gene can result in either increased or decreased aromatase activity; the associated phenotypes suggest that estrogen functions both as a sex steroid hormone and in growth or differentiation. Alternative promoter use and alternative splicing results in multiple transcript variants that have different tissue specificities. [provided by RefSeq, Dec 2016]

MIR4713HG (HGNC:53124): (MIR4713 host gene)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 15-51212614-A-C is Benign according to our data. Variant chr15-51212614-A-C is described in ClinVar as [Benign]. Clinvar id is 1247264.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP19A1	NM_000103.4	c.1022-53T>G		intron_variant		ENST00000396402.6
MIR4713HG	NR_146310.1	n.195-65369A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP19A1	ENST00000396402.6	c.1022-53T>G		intron_variant		1	NM_000103.4	P1
MIR4713HG	ENST00000559909.1	n.195-65369A>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65688 AN: 151948 Hom.: 15258 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.453

GnomAD4 exome AF: 0.495 AC: 510735 AN: 1031156 Hom.: 129680 AF XY: 0.494 AC XY: 263616 AN XY: 533440

Gnomad4 AFR exome AF: 0.242

Gnomad4 AMR exome AF: 0.330

Gnomad4 ASJ exome AF: 0.554

Gnomad4 EAS exome AF: 0.476

Gnomad4 SAS exome AF: 0.386

Gnomad4 FIN exome AF: 0.528

Gnomad4 NFE exome AF: 0.524

Gnomad4 OTH exome AF: 0.485

GnomAD4 genome AF: 0.432 AC: 65707 AN: 152066 Hom.: 15260 Cov.: 32 AF XY: 0.430 AC XY: 31961 AN XY: 74308

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.499

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.524

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.451

Alfa AF: 0.397 Hom.: 1614

Bravo AF: 0.416

Asia WGS AF: 0.386 AC: 1343 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.2
Dann	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs1065779; hg19: chr15-51504811; COSMIC: COSV53058023; COSMIC: COSV53058023;