15-90585876-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022769.5(CRTC3):c.232-7760C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 152,062 control chromosomes in the GnomAD database, including 34,587 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 0.67 (34587 hom., cov: 31)
• Consequence: CRTC3 NM_022769.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRTC3	NM_022769.5	c.232-7760C>T		intron_variant		ENST00000268184.11
CRTC3	NM_001042574.3	c.232-7760C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRTC3	ENST00000268184.11	c.232-7760C>T		intron_variant		1	NM_022769.5	P3

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102165 AN: 151944 Hom.: 34557 Cov.: 31

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.677

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

GnomAD4 genome AF: 0.672 AC: 102235 AN: 152062 Hom.: 34587 Cov.: 31 AF XY: 0.674 AC XY: 50093 AN XY: 74322

Gnomad4 AFR AF: 0.645

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.769

Gnomad4 SAS AF: 0.841

Gnomad4 FIN AF: 0.661

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.680

Alfa AF: 0.682 Hom.: 70312

Bravo AF: 0.662

Asia WGS AF: 0.781 AC: 2719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.5
Dann	Benign	0.50

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: rs6496696; hg19: chr15-91129108;