rs8031463

Variant names:

• chr15-51304342-T-C
• rs8031463
• NM_000103.4:c.-39+34153A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-51304342-T-C
• chr15-51304342-T-G

Variant summary

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

The NM_000103.4(CYP19A1):​c.-39+34153A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,084 control chromosomes in the GnomAD database, including 5,805 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 0.20 (5805 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.805
• 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]

LOC124903493 (HGNC:):

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.484 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.-39+34153A>G		intron	N/A	NP_000094.2
	CYP19A1	NM_001347248.1		c.-39+19474A>G		intron	N/A	NP_001334177.1	P11511-1
	CYP19A1	NM_001347249.2		c.-39+14091A>G		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.-39+34153A>G		intron	N/A	ENSP00000379683.1	P11511-1
	CYP19A1	ENST00000439712.6	TSL:1	n.-283+34153A>G		intron	N/A	ENSP00000390614.2	E7EQ08
	CYP19A1	ENST00000557934.5	TSL:1	n.-39+34153A>G		intron	N/A	ENSP00000454004.1	E7EQ08

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29745 AN: 151966 Hom.: 5764 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.0678

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.0804

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0474

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.196 AC: 29850 AN: 152084 Hom.: 5805 Cov.: 32 AF XY: 0.198 AC XY: 14758 AN XY: 74360

African (AFR) AF: 0.490 AC: 20287 AN: 41414

American (AMR) AF: 0.132 AC: 2016 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0678 AC: 235 AN: 3468

East Asian (EAS) AF: 0.313 AC: 1620 AN: 5168

South Asian (SAS) AF: 0.262 AC: 1263 AN: 4812

European-Finnish (FIN) AF: 0.0804 AC: 854 AN: 10620

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0474 AC: 3222 AN: 68002

Other (OTH) AF: 0.152 AC: 321 AN: 2108

Alfa AF: 0.126 Hom.: 658

Bravo AF: 0.211

Asia WGS AF: 0.328 AC: 1140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.47
PhyloP100		-0.81
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: rs8031463; hg19: chr15-51596539;