chr15-51208741-A-C

Variant names:

• chr15-51208741-A-C
• rs1042269504
• NM_000103.4:c.*2067T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000103.4(CYP19A1):​c.*2067T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (0 hom., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: CYP19A1 NM_000103.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.21
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000103.4. 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.*2067T>G		3_prime_UTR	Exon 10 of 10	NP_000094.2
	CYP19A1	NM_001347248.1		c.*2067T>G		3_prime_UTR	Exon 10 of 10	NP_001334177.1	P11511-1
	CYP19A1	NM_001347249.2		c.*2067T>G		3_prime_UTR	Exon 10 of 10	NP_001334178.1	P11511-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP19A1	ENST00000396402.6	TSL:1 MANE Select	c.*2067T>G		3_prime_UTR	Exon 10 of 10	ENSP00000379683.1	P11511-1
	MIR4713HG	ENST00000559909.1	TSL:4	n.195-69242A>C		intron	N/A
	MIR4713HG	ENST00000805692.1		n.279-69242A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00210 AC: 178 AN: 84698 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00179

Gnomad AMI AF: 0.00380

Gnomad AMR AF: 0.00158

Gnomad ASJ AF: 0.00418

Gnomad EAS AF: 0.00293

Gnomad SAS AF: 0.000825

Gnomad FIN AF: 0.000610

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00242

Gnomad OTH AF: 0.00268

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00210 AC: 178 AN: 84736 Hom.: 0 Cov.: 23 AF XY: 0.00190 AC XY: 78 AN XY: 41026

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00179 AC: 39 AN: 21802

American (AMR) AF: 0.00157 AC: 12 AN: 7620

Ashkenazi Jewish (ASJ) AF: 0.00418 AC: 9 AN: 2154

East Asian (EAS) AF: 0.00293 AC: 8 AN: 2726

South Asian (SAS) AF: 0.000827 AC: 2 AN: 2418

European-Finnish (FIN) AF: 0.000610 AC: 3 AN: 4922

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 180

European-Non Finnish (NFE) AF: 0.00242 AC: 100 AN: 41264

Other (OTH) AF: 0.00267 AC: 3 AN: 1124

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00269 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Aromatase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.62
DANN	Benign	0.49
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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: rs1042269504; hg19: chr15-51500938;