rs12915189

chr15-90571144-A-Gchr15-90571144-A-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CRTC3	NM_022769.5	c.232-22492A>G		intron_variant		ENST00000268184.11
CRTC3	NM_001042574.3	c.232-22492A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRTC3	ENST00000268184.11	c.232-22492A>G		intron_variant		1	NM_022769.5	P3

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

Gnomad4 AFR AF: 0.470

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.707

Gnomad4 FIN AF: 0.660

Gnomad4 NFE AF: 0.688

Gnomad4 OTH AF: 0.644

Alfa AF: 0.682 Hom.: 56266

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12915189; hg19: chr15-91114376; COSMIC: COSV51600210;