rs2255192

Variant names:

• chr15-51208638-C-T
• rs2255192
• NM_000103.4:c.*2170G>A

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.*2170G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 151,914 control chromosomes in the GnomAD database, including 4,751 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4751 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP19A1 NM_000103.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.781
• Publications: 13 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=-0.87).
• BP6: Variant 15-51208638-C-T is Benign according to our data. Variant chr15-51208638-C-T is described in ClinVar as Benign. ClinVar VariationId is 316447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

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.*2170G>A		3_prime_UTR	Exon 10 of 10	NP_000094.2
	CYP19A1	NM_001347248.1		c.*2170G>A		3_prime_UTR	Exon 10 of 10	NP_001334177.1	P11511-1
	CYP19A1	NM_001347249.2		c.*2170G>A		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.*2170G>A		3_prime_UTR	Exon 10 of 10	ENSP00000379683.1	P11511-1
	MIR4713HG	ENST00000559909.1	TSL:4	n.195-69345C>T		intron	N/A
	MIR4713HG	ENST00000805692.1		n.279-69345C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36727 AN: 151796 Hom.: 4746 Cov.: 30

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.216

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

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) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.242 AC: 36770 AN: 151914 Hom.: 4751 Cov.: 30 AF XY: 0.242 AC XY: 17979 AN XY: 74246

African (AFR) AF: 0.335 AC: 13850 AN: 41396

American (AMR) AF: 0.183 AC: 2801 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 750 AN: 3464

East Asian (EAS) AF: 0.184 AC: 952 AN: 5160

South Asian (SAS) AF: 0.287 AC: 1374 AN: 4792

European-Finnish (FIN) AF: 0.196 AC: 2073 AN: 10552

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14296 AN: 67956

Other (OTH) AF: 0.218 AC: 461 AN: 2114

Alfa AF: 0.220 Hom.: 16216

Bravo AF: 0.240

Asia WGS AF: 0.254 AC: 884 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Aromatase deficiency (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.27
DANN	Benign	0.71
PhyloP100		-0.78
Mutation Taster		=99/1	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2255192;

hg19: chr15-51500835;