rs4774584

Variant names:

• chr15-51269810-G-A
• rs4774584
• NM_000103.4:c.-38-26860C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-51269810-G-A
• chr15-51269810-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000103.4(CYP19A1):​c.-38-26860C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,972 control chromosomes in the GnomAD database, including 14,659 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (14659 hom., cov: 31)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.734
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000103.4. 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
	CYP19A1	NM_000103.4	MANE Select	c.-38-26860C>T		intron	N/A	NP_000094.2
	CYP19A1	NM_001347248.1		c.-38-26860C>T		intron	N/A	NP_001334177.1	P11511-1
	CYP19A1	NM_001347249.2		c.-38-26860C>T		intron	N/A	NP_001334178.1	P11511-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP19A1	ENST00000396402.6	TSL:1 MANE Select	c.-38-26860C>T		intron	N/A	ENSP00000379683.1	P11511-1
	CYP19A1	ENST00000439712.6	TSL:1	n.-282-14049C>T		intron	N/A	ENSP00000390614.2	E7EQ08
	CYP19A1	ENST00000557934.5	TSL:1	n.-38-26860C>T		intron	N/A	ENSP00000454004.1	E7EQ08

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66380 AN: 151856 Hom.: 14660 Cov.: 31

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.437

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.437 AC: 66400 AN: 151972 Hom.: 14659 Cov.: 31 AF XY: 0.432 AC XY: 32068 AN XY: 74276

African (AFR) AF: 0.459 AC: 19032 AN: 41440

American (AMR) AF: 0.361 AC: 5515 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1717 AN: 3466

East Asian (EAS) AF: 0.449 AC: 2325 AN: 5178

South Asian (SAS) AF: 0.348 AC: 1676 AN: 4812

European-Finnish (FIN) AF: 0.430 AC: 4532 AN: 10546

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.444 AC: 30139 AN: 67942

Other (OTH) AF: 0.433 AC: 916 AN: 2114

Alfa AF: 0.451 Hom.: 2522

Bravo AF: 0.433

Asia WGS AF: 0.364 AC: 1265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.53
PhyloP100		-0.73
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: rs4774584; hg19: chr15-51562007;