chr15-51218671-A-C

Variant names:

• chr15-51218671-A-C
• rs4324076
• NM_000103.4:c.629-16T>G

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.629-16T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 1,603,584 control chromosomes in the GnomAD database, including 200,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (14761 hom., cov: 32)
  • Exomes 𝑓: 0.50 (185522 hom.)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.29
• 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=-0.73).
• BP6: Variant 15-51218671-A-C is Benign according to our data. Variant chr15-51218671-A-C is described in ClinVar as Benign. ClinVar VariationId is 1174721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.629-16T>G		intron_variant	Intron 5 of 9	ENST00000396402.6	NP_000094.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.629-16T>G		intron_variant	Intron 5 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64466 AN: 151910 Hom.: 14762 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.446

GnomAD2 exomes AF: 0.453 AC: 106346 AN: 234652 AF XY: 0.459

Gnomad AFR exome AF: 0.247

Gnomad AMR exome AF: 0.318

Gnomad ASJ exome AF: 0.523

Gnomad EAS exome AF: 0.518

Gnomad FIN exome AF: 0.500

Gnomad NFE exome AF: 0.524

Gnomad OTH exome AF: 0.485

GnomAD4 exome AF: 0.500 AC: 726445 AN: 1451556 Hom.: 185522 Cov.: 62 AF XY: 0.498 AC XY: 359067 AN XY: 721224

African (AFR) AF: 0.231 AC: 7690 AN: 33326

American (AMR) AF: 0.328 AC: 14349 AN: 43782

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 13732 AN: 25860

East Asian (EAS) AF: 0.475 AC: 18731 AN: 39396

South Asian (SAS) AF: 0.360 AC: 30514 AN: 84872

European-Finnish (FIN) AF: 0.501 AC: 26106 AN: 52152

Middle Eastern (MID) AF: 0.419 AC: 2415 AN: 5758

European-Non Finnish (NFE) AF: 0.528 AC: 583916 AN: 1106400

Other (OTH) AF: 0.483 AC: 28992 AN: 60010

GnomAD4 genome AF: 0.424 AC: 64486 AN: 152028 Hom.: 14761 Cov.: 32 AF XY: 0.420 AC XY: 31242 AN XY: 74324

African (AFR) AF: 0.244 AC: 10113 AN: 41472

American (AMR) AF: 0.371 AC: 5661 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1875 AN: 3472

East Asian (EAS) AF: 0.497 AC: 2575 AN: 5184

South Asian (SAS) AF: 0.362 AC: 1744 AN: 4816

European-Finnish (FIN) AF: 0.494 AC: 5218 AN: 10564

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35763 AN: 67942

Other (OTH) AF: 0.444 AC: 937 AN: 2110

Alfa AF: 0.478 Hom.: 3823

Bravo AF: 0.410

Asia WGS AF: 0.381 AC: 1327 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:2

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.0
DANN	Benign	0.87
PhyloP100		1.3
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: rs4324076; hg19: chr15-51510868; COSMIC: COSV53058038; COSMIC: COSV53058038;