rs2305707

Variant names:

• chr15-51277213-A-G
• rs2305707
• NM_000103.4:c.-38-34263T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-51277213-A-G
• chr15-51277213-A-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.-38-34263T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,086 control chromosomes in the GnomAD database, including 6,531 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 0.25 (6531 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 18 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.-38-34263T>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.-38-34263T>C		intron_variant	Intron 1 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38273 AN: 151968 Hom.: 6510 Cov.: 32

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.218

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

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) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.252 AC: 38342 AN: 152086 Hom.: 6531 Cov.: 32 AF XY: 0.251 AC XY: 18636 AN XY: 74344

African (AFR) AF: 0.476 AC: 19714 AN: 41440

American (AMR) AF: 0.196 AC: 2995 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 448 AN: 3468

East Asian (EAS) AF: 0.309 AC: 1594 AN: 5166

South Asian (SAS) AF: 0.282 AC: 1361 AN: 4822

European-Finnish (FIN) AF: 0.141 AC: 1495 AN: 10576

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10087 AN: 67996

Other (OTH) AF: 0.223 AC: 471 AN: 2112

Alfa AF: 0.184 Hom.: 13922

Bravo AF: 0.265

Asia WGS AF: 0.335 AC: 1166 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.015
DANN	Benign	0.52
PhyloP100		-1.1
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: rs2305707; hg19: chr15-51569410;