15-51241858-T-C

Variant names:

• chr15-51241858-T-C
• rs7175531
• NM_000103.4:c.145+910A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000103.4(CYP19A1):​c.145+910A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 152,046 control chromosomes in the GnomAD database, including 36,471 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.69 (36471 hom., cov: 31)
• Consequence: CYP19A1 NM_000103.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.145+910A>G		intron_variant	Intron 2 of 9	ENST00000396402.6	NP_000094.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.145+910A>G		intron_variant	Intron 2 of 9	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104798 AN: 151928 Hom.: 36429 Cov.: 31

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.642

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.690 AC: 104897 AN: 152046 Hom.: 36471 Cov.: 31 AF XY: 0.690 AC XY: 51322 AN XY: 74328

African (AFR) AF: 0.788 AC: 32708 AN: 41500

American (AMR) AF: 0.622 AC: 9507 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2351 AN: 3470

East Asian (EAS) AF: 0.688 AC: 3517 AN: 5112

South Asian (SAS) AF: 0.749 AC: 3607 AN: 4818

European-Finnish (FIN) AF: 0.660 AC: 6983 AN: 10582

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.649 AC: 44124 AN: 67970

Other (OTH) AF: 0.642 AC: 1358 AN: 2114

Alfa AF: 0.666 Hom.: 15174

Bravo AF: 0.689

Asia WGS AF: 0.694 AC: 2415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.3
DANN	Benign	0.83
PhyloP100		0.23
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: rs7175531; hg19: chr15-51534055;