NM_000103.4:c.145+2318A>G

Variant names:

• chr15-51240450-T-C
• rs10519295
• NM_000103.4:c.145+2318A>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.145+2318A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0625 in 152,174 control chromosomes in the GnomAD database, including 443 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 0.063 (443 hom., cov: 31)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629
• Publications: 10 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.145+2318A>G		intron_variant	Intron 2 of 9	ENST00000396402.6	NP_000094.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.145+2318A>G		intron_variant	Intron 2 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.0625 AC: 9508 AN: 152056 Hom.: 443 Cov.: 31

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.0947

Gnomad AMR AF: 0.0375

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0492

Gnomad FIN AF: 0.0812

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0918

Gnomad OTH AF: 0.0608

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

GnomAD4 genome AF: 0.0625 AC: 9514 AN: 152174 Hom.: 443 Cov.: 31 AF XY: 0.0609 AC XY: 4532 AN XY: 74386

African (AFR) AF: 0.0164 AC: 682 AN: 41530

American (AMR) AF: 0.0375 AC: 573 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 666 AN: 3466

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5172

South Asian (SAS) AF: 0.0499 AC: 240 AN: 4810

European-Finnish (FIN) AF: 0.0812 AC: 860 AN: 10588

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0918 AC: 6245 AN: 68000

Other (OTH) AF: 0.0601 AC: 127 AN: 2112

Alfa AF: 0.0924 Hom.: 620

Bravo AF: 0.0562

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.62
PhyloP100		-0.63
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: rs10519295; hg19: chr15-51532647;