rs4775936

Variant names:

• chr15-51243825-C-T
• rs4775936
• NM_000103.4:c.-38-875G>A

Variant summary

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

The NM_001347254.2(CYP19A1):​c.-115G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 152,130 control chromosomes in the GnomAD database, including 11,526 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 0.36 (11526 hom., cov: 32)
• Consequence: CYP19A1 NM_001347254.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.584
• Publications: 54 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347254.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP19A1	NM_000103.4	MANE Select	c.-38-875G>A		intron	N/A	NP_000094.2
	CYP19A1	NM_001347254.2		c.-115G>A		5_prime_UTR	Exon 1 of 10	NP_001334183.1	P11511-1
	CYP19A1	NM_001347248.1		c.-38-875G>A		intron	N/A	NP_001334177.1	P11511-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP19A1	ENST00000396402.6	TSL:1 MANE Select	c.-38-875G>A		intron	N/A	ENSP00000379683.1	P11511-1
	CYP19A1	ENST00000439712.6	TSL:1	n.-38-875G>A		intron	N/A	ENSP00000390614.2	E7EQ08
	CYP19A1	ENST00000557934.5	TSL:1	n.-38-875G>A		intron	N/A	ENSP00000454004.1	E7EQ08

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54982 AN: 152012 Hom.: 11526 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.361 AC: 54982 AN: 152130 Hom.: 11526 Cov.: 32 AF XY: 0.361 AC XY: 26833 AN XY: 74372

African (AFR) AF: 0.145 AC: 6034 AN: 41530

American (AMR) AF: 0.315 AC: 4811 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1718 AN: 3470

East Asian (EAS) AF: 0.410 AC: 2123 AN: 5184

South Asian (SAS) AF: 0.351 AC: 1697 AN: 4830

European-Finnish (FIN) AF: 0.480 AC: 5065 AN: 10562

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32187 AN: 67972

Other (OTH) AF: 0.370 AC: 780 AN: 2110

Alfa AF: 0.376 Hom.: 4345

Bravo AF: 0.340

Asia WGS AF: 0.293 AC: 1021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.69
PhyloP100		0.58
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: rs4775936; hg19: chr15-51536022;