NM_000103.4:c.-38-994A>C

Variant names:

• chr15-51243944-T-G
• rs10459592
• NM_000103.4:c.-38-994A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000103.4(CYP19A1):​c.-38-994A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,996 control chromosomes in the GnomAD database, including 19,168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.49 (19168 hom., cov: 32)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.503
• Publications: 42 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 15-51243944-T-G is Benign according to our data. Variant chr15-51243944-T-G is described in ClinVar as Benign. ClinVar VariationId is 1170825.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.-38-994A>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.-38-994A>C		intron_variant	Intron 1 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75024 AN: 151878 Hom.: 19166 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.494 AC: 75053 AN: 151996 Hom.: 19168 Cov.: 32 AF XY: 0.494 AC XY: 36720 AN XY: 74300

African (AFR) AF: 0.353 AC: 14628 AN: 41444

American (AMR) AF: 0.510 AC: 7789 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1987 AN: 3470

East Asian (EAS) AF: 0.423 AC: 2188 AN: 5170

South Asian (SAS) AF: 0.494 AC: 2375 AN: 4810

European-Finnish (FIN) AF: 0.567 AC: 6002 AN: 10578

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38385 AN: 67938

Other (OTH) AF: 0.491 AC: 1036 AN: 2108

Alfa AF: 0.540 Hom.: 63277

Bravo AF: 0.482

Asia WGS AF: 0.376 AC: 1310 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 15, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.89
DANN	Benign	0.83
PhyloP100		-0.50
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: rs10459592; hg19: chr15-51536141;