rs2305707

Positions:

• chr15-51277213-A-G
• chr15-51277213-A-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CYP19A1	NM_000103.4	c.-38-34263T>C		intron_variant		ENST00000396402.6
MIR4713HG	NR_146310.1	n.195-770A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP19A1	ENST00000396402.6	c.-38-34263T>C		intron_variant		1	NM_000103.4	P1
MIR4713HG	ENST00000559909.1	n.195-770A>G		intron_variant, non_coding_transcript_variant		4

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

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

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.223

Alfa AF: 0.169 Hom.: 5335

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2305707; hg19: chr15-51569410;