chr15-51208549-A-AT

Position:

• chr15-51208549-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000103.4(CYP19A1):​c.*2258_*2259insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (16488 hom., cov: 0)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: CYP19A1 NM_000103.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.142

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 -10 ACMG points.

• BP6: Variant 15-51208549-A-AT is Benign according to our data. Variant chr15-51208549-A-AT is described in ClinVar as [Benign]. Clinvar id is 316444.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.*2258_*2259insA		3_prime_UTR_variant	10/10	ENST00000396402.6
MIR4713HG	NR_146310.1	n.195-69434_195-69433insT		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP19A1	ENST00000396402.6	c.*2258_*2259insA		3_prime_UTR_variant	10/10	1	NM_000103.4	P1
MIR4713HG	ENST00000559909.1	n.195-69434_195-69433insT		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69620 AN: 151802 Hom.: 16487 Cov.: 0

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.466

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 AFR exome AF: 0.500

GnomAD4 genome AF: 0.458 AC: 69648 AN: 151920 Hom.: 16488 Cov.: 0 AF XY: 0.454 AC XY: 33754 AN XY: 74276

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.464

Alfa AF: 0.507 Hom.: 2421

Bravo AF: 0.448

Asia WGS AF: 0.382 AC: 1329 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Aromatase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs3217422; hg19: chr15-51500746; COSMIC: COSV53057872; COSMIC: COSV53057872;