rs11856927

Variant names:

• chr15-51256508-G-T
• rs11856927
• NM_000103.4:c.-38-13558C>A

Variant summary

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

The NM_000103.4(CYP19A1):​c.-38-13558C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,878 control chromosomes in the GnomAD database, including 25,981 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 0.58 (25981 hom., cov: 31)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.882
• Publications: 13 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 (SAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.-38-13558C>A		intron_variant	Intron 1 of 9	ENST00000396402.6	NP_000094.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.-38-13558C>A		intron_variant	Intron 1 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88202 AN: 151760 Hom.: 25952 Cov.: 31

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.581 AC: 88288 AN: 151878 Hom.: 25981 Cov.: 31 AF XY: 0.586 AC XY: 43517 AN XY: 74204

African (AFR) AF: 0.526 AC: 21791 AN: 41394

American (AMR) AF: 0.696 AC: 10628 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1912 AN: 3470

East Asian (EAS) AF: 0.559 AC: 2890 AN: 5170

South Asian (SAS) AF: 0.696 AC: 3346 AN: 4806

European-Finnish (FIN) AF: 0.568 AC: 5973 AN: 10524

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.586 AC: 39800 AN: 67942

Other (OTH) AF: 0.605 AC: 1275 AN: 2106

Alfa AF: 0.560 Hom.: 3108

Bravo AF: 0.588

Asia WGS AF: 0.676 AC: 2350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.037
DANN	Benign	0.46
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11856927; hg19: chr15-51548705;