rs12915189

Variant names:

• chr15-90571144-A-G
• rs12915189
• NM_022769.5:c.232-22492A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-90571144-A-G
• chr15-90571144-A-T

Variant summary

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

The NM_022769.5(CRTC3):​c.232-22492A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 152,082 control chromosomes in the GnomAD database, including 29,688 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 0.62 (29688 hom., cov: 32)
• Consequence: CRTC3 NM_022769.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• Publications: 19 publications found

Genes affected

CRTC3 (HGNC:26148): (CREB regulated transcription coactivator 3) This gene is a member of the CREB regulated transcription coactivator gene family. This family regulates CREB-dependent gene transcription in a phosphorylation-independent manner and may be selective for cAMP-responsive genes. The protein encoded by this gene may induce mitochondrial biogenesis and attenuate catecholamine signaling in adipose tissue. A translocation event between this gene and Notch coactivator mastermind-like gene 2, which results in a fusion protein, has been reported in mucoepidermoid carcinomas. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTC3	NM_022769.5	c.232-22492A>G		intron_variant	Intron 2 of 14	ENST00000268184.11	NP_073606.3
CRTC3	NM_001042574.3	c.232-22492A>G		intron_variant	Intron 2 of 14		NP_001036039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTC3	ENST00000268184.11	c.232-22492A>G		intron_variant	Intron 2 of 14	1	NM_022769.5	ENSP00000268184.6
CRTC3	ENST00000420329.6	c.232-22492A>G		intron_variant	Intron 2 of 14	2		ENSP00000416573.2
CRTC3	ENST00000686240.1	n.232-22492A>G		intron_variant	Intron 2 of 13			ENSP00000508866.1
CRTC3	ENST00000687075.1	n.55-22492A>G		intron_variant	Intron 1 of 8			ENSP00000510590.1
CRTC3	ENST00000691029.1	n.232-22492A>G		intron_variant	Intron 2 of 16			ENSP00000510507.1
CRTC3	ENST00000692149.1	n.232-22492A>G		intron_variant	Intron 2 of 12			ENSP00000510448.1

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93782 AN: 151964 Hom.: 29676 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.642

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

GnomAD4 genome AF: 0.617 AC: 93830 AN: 152082 Hom.: 29688 Cov.: 32 AF XY: 0.616 AC XY: 45822 AN XY: 74352

African (AFR) AF: 0.470 AC: 19494 AN: 41472

American (AMR) AF: 0.605 AC: 9244 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 2496 AN: 3470

East Asian (EAS) AF: 0.620 AC: 3208 AN: 5174

South Asian (SAS) AF: 0.707 AC: 3412 AN: 4826

European-Finnish (FIN) AF: 0.660 AC: 6977 AN: 10566

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.688 AC: 46792 AN: 67978

Other (OTH) AF: 0.644 AC: 1362 AN: 2114

Alfa AF: 0.668 Hom.: 85914

Bravo AF: 0.603

Asia WGS AF: 0.651 AC: 2267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.034
DANN	Benign	0.57
PhyloP100		-1.8
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: rs12915189; hg19: chr15-91114376; COSMIC: COSV51600210;