rs1004984

Positions:

• chr15-51321332-G-A
• chr15-51321332-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000103.4(CYP19A1):​c.-39+17163C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 151,742 control chromosomes in the GnomAD database, including 12,486 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 0.40 (12486 hom., cov: 31)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.00

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.-39+17163C>T		intron_variant		ENST00000396402.6	NP_000094.2
LOC112268146	XR_002957708.2	n.1113-277G>A		intron_variant, non_coding_transcript_variant
CYP19A1	NM_001347248.1	c.-39+2484C>T		intron_variant			NP_001334177.1
CYP19A1	NM_031226.3	c.-39+2484C>T		intron_variant			NP_112503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.-39+17163C>T		intron_variant		1	NM_000103.4	ENSP00000379683	P1
	ENST00000559672.2	n.389-277G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60370 AN: 151624 Hom.: 12450 Cov.: 31

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.398 AC: 60455 AN: 151742 Hom.: 12486 Cov.: 31 AF XY: 0.395 AC XY: 29283 AN XY: 74132

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.466

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.412

Alfa AF: 0.383 Hom.: 12607

Bravo AF: 0.421

Asia WGS AF: 0.424 AC: 1475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.41
DANN	Benign	0.17

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: rs1004984; hg19: chr15-51613529;