ENST00000478421.1:n.44A>T

Variant names:

• chr15-51218505-T-A
• rs1143704
• ENST00000478421.1:n.44A>T

Variant summary

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

The ENST00000478421.1(CYP19A1):​n.44A>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 1,589,230 control chromosomes in the GnomAD database, including 198,649 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (14716 hom., cov: 32)
  • Exomes 𝑓: 0.50 (183933 hom.)
• Consequence: CYP19A1 ENST00000478421.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.184
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.10286E-5).
• BP6: Variant 15-51218505-T-A is Benign according to our data. Variant chr15-51218505-T-A is described in ClinVar as Benign. ClinVar VariationId is 1168854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000478421.1. 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
	CYP19A1	NM_000103.4	MANE Select	c.743+36A>T		intron	N/A	NP_000094.2
	CYP19A1	NM_001347248.1		c.743+36A>T		intron	N/A	NP_001334177.1
	CYP19A1	NM_001347249.2		c.743+36A>T		intron	N/A	NP_001334178.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP19A1	ENST00000478421.1	TSL:1	n.44A>T		non_coding_transcript_exon	Exon 1 of 2
	CYP19A1	ENST00000396402.6	TSL:1 MANE Select	c.743+36A>T		intron	N/A	ENSP00000379683.1
	CYP19A1	ENST00000559878.5	TSL:1	c.743+36A>T		intron	N/A	ENSP00000453149.1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64367 AN: 151910 Hom.: 14718 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.444

GnomAD2 exomes AF: 0.450 AC: 97867 AN: 217604 AF XY: 0.455

Gnomad AFR exome AF: 0.241

Gnomad AMR exome AF: 0.315

Gnomad ASJ exome AF: 0.523

Gnomad EAS exome AF: 0.517

Gnomad FIN exome AF: 0.500

Gnomad NFE exome AF: 0.521

Gnomad OTH exome AF: 0.485

GnomAD4 exome AF: 0.501 AC: 719591 AN: 1437200 Hom.: 183933 Cov.: 39 AF XY: 0.498 AC XY: 354910 AN XY: 712698

African (AFR) AF: 0.228 AC: 7483 AN: 32822

American (AMR) AF: 0.327 AC: 13792 AN: 42152

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 13605 AN: 25614

East Asian (EAS) AF: 0.475 AC: 18429 AN: 38832

South Asian (SAS) AF: 0.359 AC: 29808 AN: 82988

European-Finnish (FIN) AF: 0.501 AC: 26010 AN: 51914

Middle Eastern (MID) AF: 0.420 AC: 2150 AN: 5116

European-Non Finnish (NFE) AF: 0.528 AC: 579676 AN: 1098416

Other (OTH) AF: 0.483 AC: 28638 AN: 59346

GnomAD4 genome AF: 0.423 AC: 64382 AN: 152030 Hom.: 14716 Cov.: 32 AF XY: 0.420 AC XY: 31179 AN XY: 74306

African (AFR) AF: 0.242 AC: 10013 AN: 41452

American (AMR) AF: 0.371 AC: 5672 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1875 AN: 3472

East Asian (EAS) AF: 0.497 AC: 2565 AN: 5162

South Asian (SAS) AF: 0.362 AC: 1740 AN: 4808

European-Finnish (FIN) AF: 0.494 AC: 5224 AN: 10580

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35757 AN: 67956

Other (OTH) AF: 0.442 AC: 936 AN: 2116

Alfa AF: 0.491 Hom.: 3498

Bravo AF: 0.409

TwinsUK AF: 0.541 AC: 2007

ALSPAC AF: 0.525 AC: 2022

ESP6500AA AF: 0.246 AC: 1081

ESP6500EA AF: 0.519 AC: 4452

ExAC AF: 0.430 AC: 51739

Asia WGS AF: 0.379 AC: 1318 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Nov 15, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 16882736)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.3
DANN	Benign	0.83
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.000041	T
PhyloP100		-0.18
GERP RS		-3.8
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: rs1143704; hg19: chr15-51510702; COSMIC: COSV53058074; COSMIC: COSV53058074;