rs1065779

Variant names:

• chr15-51212614-A-C
• rs1065779
• NM_000103.4:c.1022-53T>G

Your query was ambiguous. Multiple possible variants found:

• chr15-51212614-A-C
• chr15-51212614-A-T

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.1022-53T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 1,183,222 control chromosomes in the GnomAD database, including 144,940 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (15260 hom., cov: 32)
  • Exomes 𝑓: 0.50 (129680 hom.)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.802
• Publications: 16 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=-0.83).
• BP6: Variant 15-51212614-A-C is Benign according to our data. Variant chr15-51212614-A-C is described in ClinVar as Benign. ClinVar VariationId is 1247264.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.1022-53T>G		intron	N/A	NP_000094.2
	CYP19A1	NM_001347248.1		c.1022-53T>G		intron	N/A	NP_001334177.1	P11511-1
	CYP19A1	NM_001347249.2		c.1022-53T>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.1022-53T>G		intron	N/A	ENSP00000379683.1	P11511-1
	CYP19A1	ENST00000559878.5	TSL:1	c.1022-53T>G		intron	N/A	ENSP00000453149.1	P11511-1
	CYP19A1	ENST00000439712.6	TSL:1	n.1022-53T>G		intron	N/A	ENSP00000390614.2	E7EQ08

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65688 AN: 151948 Hom.: 15258 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.453

GnomAD4 exome AF: 0.495 AC: 510735 AN: 1031156 Hom.: 129680 AF XY: 0.494 AC XY: 263616 AN XY: 533440

African (AFR) AF: 0.242 AC: 6145 AN: 25348

American (AMR) AF: 0.330 AC: 14559 AN: 44076

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 13000 AN: 23478

East Asian (EAS) AF: 0.476 AC: 17924 AN: 37692

South Asian (SAS) AF: 0.386 AC: 30024 AN: 77752

European-Finnish (FIN) AF: 0.528 AC: 26764 AN: 50684

Middle Eastern (MID) AF: 0.425 AC: 1918 AN: 4510

European-Non Finnish (NFE) AF: 0.524 AC: 377967 AN: 721366

Other (OTH) AF: 0.485 AC: 22434 AN: 46250

GnomAD4 genome AF: 0.432 AC: 65707 AN: 152066 Hom.: 15260 Cov.: 32 AF XY: 0.430 AC XY: 31961 AN XY: 74308

African (AFR) AF: 0.255 AC: 10569 AN: 41470

American (AMR) AF: 0.376 AC: 5742 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1959 AN: 3470

East Asian (EAS) AF: 0.499 AC: 2573 AN: 5160

South Asian (SAS) AF: 0.392 AC: 1891 AN: 4826

European-Finnish (FIN) AF: 0.524 AC: 5532 AN: 10554

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35885 AN: 67978

Other (OTH) AF: 0.451 AC: 955 AN: 2116

Alfa AF: 0.391 Hom.: 1643

Bravo AF: 0.416

Asia WGS AF: 0.386 AC: 1343 AN: 3478

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	-0.83
CADD	Benign	2.2
DANN	Benign	0.61
PhyloP100		0.80
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: rs1065779; hg19: chr15-51504811; COSMIC: COSV53058023; COSMIC: COSV53058023;