rs2008691

Variant names:

• chr15-51256113-A-G
• rs2008691
• NM_000103.4:c.-38-13163T>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.-38-13163T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,234 control chromosomes in the GnomAD database, including 4,959 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 0.23 (4959 hom., cov: 33)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• Publications: 21 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.-38-13163T>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.-38-13163T>C		intron_variant	Intron 1 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34544 AN: 152116 Hom.: 4932 Cov.: 33

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.227 AC: 34622 AN: 152234 Hom.: 4959 Cov.: 33 AF XY: 0.228 AC XY: 16995 AN XY: 74434

African (AFR) AF: 0.401 AC: 16663 AN: 41518

American (AMR) AF: 0.150 AC: 2297 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 456 AN: 3472

East Asian (EAS) AF: 0.264 AC: 1370 AN: 5180

South Asian (SAS) AF: 0.286 AC: 1376 AN: 4816

European-Finnish (FIN) AF: 0.162 AC: 1720 AN: 10598

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10138 AN: 68030

Other (OTH) AF: 0.191 AC: 404 AN: 2110

Alfa AF: 0.170 Hom.: 4421

Bravo AF: 0.231

Asia WGS AF: 0.319 AC: 1108 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	6.6
DANN	Benign	0.59
PhyloP100		-0.18
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: rs2008691; hg19: chr15-51548310;