rs2289105

Variant names:

• chr15-51215311-T-C
• rs2289105
• NM_000103.4:c.859-79A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-51215311-T-C
• chr15-51215311-T-A
• chr15-51215311-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000103.4(CYP19A1):​c.859-79A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 1,593,508 control chromosomes in the GnomAD database, including 202,918 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (15031 hom., cov: 32)
  • Exomes 𝑓: 0.51 (187887 hom.)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.112
• Publications: 23 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 15-51215311-T-C is Benign according to our data. Variant chr15-51215311-T-C is described in ClinVar as Benign. ClinVar VariationId is 1293222.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.523 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP19A1	NM_000103.4	MANE Select	c.859-79A>G		intron	N/A	NP_000094.2
	CYP19A1	NM_001347248.1		c.859-79A>G		intron	N/A	NP_001334177.1	P11511-1
	CYP19A1	NM_001347249.2		c.859-79A>G		intron	N/A	NP_001334178.1	P11511-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP19A1	ENST00000396402.6	TSL:1 MANE Select	c.859-79A>G		intron	N/A	ENSP00000379683.1	P11511-1
	CYP19A1	ENST00000559878.5	TSL:1	c.859-79A>G		intron	N/A	ENSP00000453149.1	P11511-1
	CYP19A1	ENST00000439712.6	TSL:1	n.859-79A>G		intron	N/A	ENSP00000390614.2	E7EQ08

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64752 AN: 151898 Hom.: 15032 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.450

GnomAD4 exome AF: 0.506 AC: 729114 AN: 1441492 Hom.: 187887 AF XY: 0.504 AC XY: 361626 AN XY: 717844

African (AFR) AF: 0.221 AC: 7268 AN: 32936

American (AMR) AF: 0.330 AC: 14647 AN: 44354

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 14495 AN: 26032

East Asian (EAS) AF: 0.481 AC: 18886 AN: 39290

South Asian (SAS) AF: 0.388 AC: 33106 AN: 85320

European-Finnish (FIN) AF: 0.529 AC: 26815 AN: 50664

Middle Eastern (MID) AF: 0.433 AC: 2475 AN: 5718

European-Non Finnish (NFE) AF: 0.530 AC: 582230 AN: 1097538

Other (OTH) AF: 0.489 AC: 29192 AN: 59640

GnomAD4 genome AF: 0.426 AC: 64765 AN: 152016 Hom.: 15031 Cov.: 32 AF XY: 0.424 AC XY: 31520 AN XY: 74300

African (AFR) AF: 0.233 AC: 9663 AN: 41450

American (AMR) AF: 0.372 AC: 5684 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1961 AN: 3470

East Asian (EAS) AF: 0.501 AC: 2591 AN: 5172

South Asian (SAS) AF: 0.393 AC: 1891 AN: 4816

European-Finnish (FIN) AF: 0.524 AC: 5535 AN: 10556

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

European-Non Finnish (NFE) AF: 0.528 AC: 35888 AN: 67970

Other (OTH) AF: 0.448 AC: 948 AN: 2116

Alfa AF: 0.489 Hom.: 19231

Bravo AF: 0.409

Asia WGS AF: 0.387 AC: 1347 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.9
DANN	Benign	0.47
PhyloP100		-0.11
PromoterAI		-0.012	Neutral
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: rs2289105; hg19: chr15-51507508; COSMIC: COSV53058026; COSMIC: COSV53058026;