15-51313211-A-G

Variant names:

• chr15-51313211-A-G
• rs16964258
• NM_000103.4:c.-39+25284T>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.-39+25284T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,264 control chromosomes in the GnomAD database, including 5,870 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 (5870 hom., cov: 33)
  • Exomes 𝑓: 0.042 (0 hom.)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76
• Publications: 8 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=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.-39+25284T>C		intron_variant	Intron 1 of 9	ENST00000396402.6	NP_000094.2
CYP19A1	NM_001347248.1	c.-39+10605T>C		intron_variant	Intron 1 of 9		NP_001334177.1
CYP19A1	NM_001347249.2	c.-39+5222T>C		intron_variant	Intron 1 of 9		NP_001334178.1
CYP19A1	NM_031226.3	c.-39+10605T>C		intron_variant	Intron 2 of 10		NP_112503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.-39+25284T>C		intron_variant	Intron 1 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 30012 AN: 152122 Hom.: 5829 Cov.: 33

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.0817

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0488

Gnomad OTH AF: 0.147

GnomAD4 exome AF: 0.0417 AC: 1 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.0500 AC XY: 1 AN XY: 20

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 18

Other (OTH) AF: 0.167 AC: 1 AN: 6

GnomAD4 genome AF: 0.198 AC: 30117 AN: 152240 Hom.: 5870 Cov.: 33 AF XY: 0.200 AC XY: 14889 AN XY: 74446

African (AFR) AF: 0.491 AC: 20395 AN: 41496

American (AMR) AF: 0.132 AC: 2027 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0674 AC: 234 AN: 3472

East Asian (EAS) AF: 0.318 AC: 1645 AN: 5180

South Asian (SAS) AF: 0.263 AC: 1272 AN: 4830

European-Finnish (FIN) AF: 0.0817 AC: 868 AN: 10618

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.0487 AC: 3316 AN: 68024

Other (OTH) AF: 0.155 AC: 327 AN: 2114

Alfa AF: 0.168 Hom.: 870

Bravo AF: 0.212

Asia WGS AF: 0.335 AC: 1164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.71
PhyloP100		1.8
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: rs16964258; hg19: chr15-51605408;