rs17601241

Variant names:

• chr15-51215677-G-A
• rs17601241
• NM_000103.4:c.858+26C>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.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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.104
• Publications: 15 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=-0.84).
• BP6: Variant 15-51215677-G-A is Benign according to our data. Variant chr15-51215677-G-A is described in ClinVar as Benign. ClinVar VariationId is 1293221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.858+26C>T		intron_variant	Intron 7 of 9	ENST00000396402.6	NP_000094.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.858+26C>T		intron_variant	Intron 7 of 9	1	NM_000103.4	ENSP00000379683.1

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

GnomAD2 exomes AF: 0.106 AC: 26610 AN: 251074 AF XY: 0.105

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 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

African (AFR) AF: 0.0500 AC: 1672 AN: 33458

American (AMR) AF: 0.210 AC: 9407 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0868 AC: 2269 AN: 26126

East Asian (EAS) AF: 0.00812 AC: 322 AN: 39654

South Asian (SAS) AF: 0.147 AC: 12664 AN: 86246

European-Finnish (FIN) AF: 0.0849 AC: 4526 AN: 53326

Middle Eastern (MID) AF: 0.0837 AC: 482 AN: 5762

European-Non Finnish (NFE) AF: 0.0900 AC: 100056 AN: 1111888

Other (OTH) AF: 0.0888 AC: 5363 AN: 60374

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

African (AFR) AF: 0.0513 AC: 2131 AN: 41526

American (AMR) AF: 0.179 AC: 2731 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0789 AC: 274 AN: 3472

East Asian (EAS) AF: 0.0108 AC: 56 AN: 5178

South Asian (SAS) AF: 0.143 AC: 692 AN: 4826

European-Finnish (FIN) AF: 0.0881 AC: 934 AN: 10596

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0886 AC: 6027 AN: 68000

Other (OTH) AF: 0.0909 AC: 192 AN: 2112

Alfa AF: 0.0900 Hom.: 2090

Bravo AF: 0.0915

Asia WGS AF: 0.0710 AC: 248 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.5
DANN	Benign	0.30
PhyloP100		0.10
PromoterAI		0.0038	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: rs17601241; hg19: chr15-51507874; COSMIC: COSV53063542; COSMIC: COSV53063542;