rs17601241

chr15-51215677-G-A

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.858+26C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0929 in 1,613,754 control chromosomes in the GnomAD database, including 8,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.086 (710 hom., cov: 33)
  • Exomes 𝑓: 0.094 (7339 hom.)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.104

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=-0.84).
• BP6: Variant 15-51215677-G-A is Benign according to our data. Variant chr15-51215677-G-A is described in ClinVar as [Benign]. Clinvar id is 1293221.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP19A1	NM_000103.4	c.858+26C>T		intron_variant		ENST00000396402.6
MIR4713HG	NR_146310.1	n.195-62306G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP19A1	ENST00000396402.6	c.858+26C>T		intron_variant		1	NM_000103.4	P1
MIR4713HG	ENST00000559909.1	n.195-62306G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0864 AC: 13135 AN: 152090 Hom.: 711 Cov.: 33

Gnomad AFR AF: 0.0514

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.0789

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0881

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0887

Gnomad OTH AF: 0.0919

GnomAD3 exomes AF: 0.106 AC: 26610 AN: 251074 Hom.: 1857 AF XY: 0.105 AC XY: 14195 AN XY: 135714

Gnomad AFR exome AF: 0.0492

Gnomad AMR exome AF: 0.217

Gnomad ASJ exome AF: 0.0874

Gnomad EAS exome AF: 0.00882

Gnomad SAS exome AF: 0.144

Gnomad FIN exome AF: 0.0844

Gnomad NFE exome AF: 0.0923

Gnomad OTH exome AF: 0.0883

GnomAD4 exome AF: 0.0936 AC: 136761 AN: 1461546 Hom.: 7339 Cov.: 35 AF XY: 0.0945 AC XY: 68707 AN XY: 727066

Gnomad4 AFR exome AF: 0.0500

Gnomad4 AMR exome AF: 0.210

Gnomad4 ASJ exome AF: 0.0868

Gnomad4 EAS exome AF: 0.00812

Gnomad4 SAS exome AF: 0.147

Gnomad4 FIN exome AF: 0.0849

Gnomad4 NFE exome AF: 0.0900

Gnomad4 OTH exome AF: 0.0888

GnomAD4 genome AF: 0.0863 AC: 13134 AN: 152208 Hom.: 710 Cov.: 33 AF XY: 0.0898 AC XY: 6686 AN XY: 74414

Gnomad4 AFR AF: 0.0513

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.0789

Gnomad4 EAS AF: 0.0108

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.0881

Gnomad4 NFE AF: 0.0886

Gnomad4 OTH AF: 0.0909

Alfa AF: 0.0934 Hom.: 833

Bravo AF: 0.0915

Asia WGS AF: 0.0710 AC: 248 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

GeneDx

Mar 03, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.5
Dann	Benign	0.30

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

Publications

LitVar

Other links and lift over

dbSNP: rs17601241; hg19: chr15-51507874; COSMIC: COSV53063542; COSMIC: COSV53063542;