NM_000103.4:c.-38-43447T>C

Variant names:

• chr15-51286397-A-G
• rs7167343
• NM_000103.4:c.-38-43447T>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.-38-43447T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,074 control chromosomes in the GnomAD database, including 2,987 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 0.15 (2987 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 4 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 = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.-38-43447T>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.-38-43447T>C		intron_variant	Intron 1 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22041 AN: 151956 Hom.: 2967 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0547

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.0782

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0413

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.145 AC: 22116 AN: 152074 Hom.: 2987 Cov.: 32 AF XY: 0.148 AC XY: 11029 AN XY: 74336

African (AFR) AF: 0.348 AC: 14422 AN: 41452

American (AMR) AF: 0.112 AC: 1720 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0547 AC: 190 AN: 3472

East Asian (EAS) AF: 0.171 AC: 884 AN: 5160

South Asian (SAS) AF: 0.209 AC: 1004 AN: 4804

European-Finnish (FIN) AF: 0.0782 AC: 828 AN: 10582

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0413 AC: 2808 AN: 67992

Other (OTH) AF: 0.114 AC: 240 AN: 2114

Alfa AF: 0.0772 Hom.: 2800

Bravo AF: 0.155

Asia WGS AF: 0.237 AC: 823 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.75
PhyloP100		1.0
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: rs7167343; hg19: chr15-51578594;