NM_000103.4:c.-38-36890C>T

Variant names:

• chr15-51279840-G-A
• rs8029807
• NM_000103.4:c.-38-36890C>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.-38-36890C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.097 in 152,282 control chromosomes in the GnomAD database, including 819 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 0.097 (819 hom., cov: 32)
  • Exomes 𝑓: 0.063 (0 hom.)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• 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)

ENSG00000259701 (HGNC:):

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 = 0.123 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000103.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP19A1	NM_000103.4	MANE Select	c.-38-36890C>T		intron	N/A	NP_000094.2
	CYP19A1	NM_001347248.1		c.-38-36890C>T		intron	N/A	NP_001334177.1
	CYP19A1	NM_001347249.2		c.-38-36890C>T		intron	N/A	NP_001334178.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP19A1	ENST00000396402.6	TSL:1 MANE Select	c.-38-36890C>T		intron	N/A	ENSP00000379683.1
	CYP19A1	ENST00000439712.6	TSL:1	n.-282-24079C>T		intron	N/A	ENSP00000390614.2
	CYP19A1	ENST00000557934.5	TSL:1	n.-38-36890C>T		intron	N/A	ENSP00000454004.1

Frequencies

GnomAD3 genomes AF: 0.0971 AC: 14770 AN: 152148 Hom.: 819 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.0751

Gnomad ASJ AF: 0.0606

Gnomad EAS AF: 0.00577

Gnomad SAS AF: 0.0475

Gnomad FIN AF: 0.0603

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.100

GnomAD4 exome AF: 0.0625 AC: 1 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.0833 AC XY: 1 AN XY: 12

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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) AF: 0.167 AC: 1 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AF: 0.00 AC: 0 AN: 2

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0970 AC: 14768 AN: 152266 Hom.: 819 Cov.: 32 AF XY: 0.0917 AC XY: 6830 AN XY: 74444

African (AFR) AF: 0.126 AC: 5243 AN: 41544

American (AMR) AF: 0.0750 AC: 1147 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0606 AC: 210 AN: 3468

East Asian (EAS) AF: 0.00578 AC: 30 AN: 5188

South Asian (SAS) AF: 0.0477 AC: 230 AN: 4822

European-Finnish (FIN) AF: 0.0603 AC: 640 AN: 10614

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6912 AN: 68012

Other (OTH) AF: 0.0985 AC: 208 AN: 2112

Alfa AF: 0.0988 Hom.: 3176

Bravo AF: 0.0995

Asia WGS AF: 0.0320 AC: 111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.32
DANN	Benign	0.67
PhyloP100		-1.2
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: rs8029807; hg19: chr15-51572037;