rs1062033

Positions:

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

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000103.4(CYP19A1):​c.-38-12791G>C variant causes a intron 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_000103.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.982

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

Verdict is Benign. Variant got -14 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 id is 1170826.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP19A1	NM_000103.4	c.-38-12791G>C		intron_variant		ENST00000396402.6
MIR4713HG	NR_146310.1	n.195-22242C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP19A1	ENST00000396402.6	c.-38-12791G>C		intron_variant		1	NM_000103.4	P1
MIR4713HG	ENST00000559909.1	n.195-22242C>G		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR exome AF: 0.500

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.500

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

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.349

Alfa AF: 0.415 Hom.: 1988

Bravo AF: 0.329

Asia WGS AF: 0.291 AC: 1012 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.44
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs1062033; hg19: chr15-51547938;