rs7181886

Variant names:

• chr15-51282108-C-G
• rs7181886
• NM_000103.4:c.-38-39158G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-51282108-C-G
• chr15-51282108-C-T

Variant summary

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

The NM_000103.4(CYP19A1):​c.-38-39158G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 145,994 control chromosomes in the GnomAD database, including 2,102 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 0.13 (2102 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127
• Publications: 5 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.-38-39158G>C		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.-38-39158G>C		intron_variant	Intron 1 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 19188 AN: 145884 Hom.: 2087 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0524

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.0786

Gnomad MID AF: 0.0548

Gnomad NFE AF: 0.0415

Gnomad OTH AF: 0.0945

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

GnomAD4 genome AF: 0.132 AC: 19250 AN: 145994 Hom.: 2102 Cov.: 32 AF XY: 0.135 AC XY: 9662 AN XY: 71362

African (AFR) AF: 0.308 AC: 11732 AN: 38032

American (AMR) AF: 0.108 AC: 1608 AN: 14944

Ashkenazi Jewish (ASJ) AF: 0.0524 AC: 177 AN: 3380

East Asian (EAS) AF: 0.218 AC: 885 AN: 4068

South Asian (SAS) AF: 0.224 AC: 1000 AN: 4466

European-Finnish (FIN) AF: 0.0786 AC: 829 AN: 10550

Middle Eastern (MID) AF: 0.0551 AC: 15 AN: 272

European-Non Finnish (NFE) AF: 0.0415 AC: 2795 AN: 67328

Other (OTH) AF: 0.100 AC: 205 AN: 2042

Alfa AF: 0.0222 Hom.: 21

Bravo AF: 0.134

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.77
DANN	Benign	0.74
PhyloP100		-0.13
Mutation Taster		=99/1	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: rs7181886; hg19: chr15-51574305;