rs1062033

Variant names:

• chr15-51255741-C-G
• rs1062033
• NM_000103.4:c.-38-12791G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-51255741-C-G
• chr15-51255741-C-T

Variant summary

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

The NM_001347253.2(CYP19A1):​c.-262G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 152,172 control chromosomes in the GnomAD database, including 10,911 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (10910 hom., cov: 32)
  • Exomes 𝑓: 0.40 (1 hom.)
• Consequence: CYP19A1 NM_001347253.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.982
• Publications: 43 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=-0.86).
• BP6: Variant 15-51255741-C-G is Benign according to our data. Variant chr15-51255741-C-G is described in ClinVar as Benign. ClinVar VariationId is 1170826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347253.2. 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.-38-12791G>C		intron	N/A	NP_000094.2
	CYP19A1	NM_001347253.2		c.-262G>C		5_prime_UTR	Exon 1 of 10	NP_001334182.1	P11511-1
	CYP19A1	NM_001347248.1		c.-38-12791G>C		intron	N/A	NP_001334177.1	P11511-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP19A1	ENST00000396402.6	TSL:1 MANE Select	c.-38-12791G>C		intron	N/A	ENSP00000379683.1	P11511-1
	CYP19A1	ENST00000439712.6	TSL:1	n.-262G>C		non_coding_transcript_exon	Exon 2 of 10	ENSP00000390614.2	E7EQ08
	CYP19A1	ENST00000439712.6	TSL:1	n.-262G>C		5_prime_UTR	Exon 2 of 10	ENSP00000390614.2	E7EQ08

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53321 AN: 152034 Hom.: 10909 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.354

GnomAD4 exome AF: 0.400 AC: 8 AN: 20 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 6 AN XY: 12

African (AFR) AF: 0.500 AC: 1 AN: 2

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) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.375 AC: 6 AN: 16

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.351 AC: 53331 AN: 152152 Hom.: 10910 Cov.: 32 AF XY: 0.350 AC XY: 26014 AN XY: 74392

African (AFR) AF: 0.141 AC: 5875 AN: 41526

American (AMR) AF: 0.310 AC: 4736 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1661 AN: 3466

East Asian (EAS) AF: 0.419 AC: 2168 AN: 5172

South Asian (SAS) AF: 0.299 AC: 1443 AN: 4824

European-Finnish (FIN) AF: 0.481 AC: 5082 AN: 10574

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31093 AN: 67996

Other (OTH) AF: 0.349 AC: 739 AN: 2116

Alfa AF: 0.415 Hom.: 1988

Bravo AF: 0.329

Asia WGS AF: 0.291 AC: 1012 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	-0.86
CADD	Benign	0.44
DANN	Benign	0.41
PhyloP100		-0.98
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs1062033; hg19: chr15-51547938;