rs7495132

Positions:

• chr15-90629669-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.1266+137C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 733,698 control chromosomes in the GnomAD database, including 5,283 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 0.12 (1303 hom., cov: 32)
  • Exomes 𝑓: 0.11 (3980 hom.)
• Consequence: CRTC3 NM_022769.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.424

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]

CRTC3-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRTC3	NM_022769.5	c.1266+137C>T		intron_variant		ENST00000268184.11	NP_073606.3
CRTC3	NM_001042574.3	c.1266+137C>T		intron_variant			NP_001036039.1
CRTC3-AS1	NR_120372.1	n.510-9516G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRTC3	ENST00000268184.11	c.1266+137C>T		intron_variant		1	NM_022769.5	ENSP00000268184.6
CRTC3	ENST00000420329.6	c.1266+137C>T		intron_variant		2		ENSP00000416573.2
CRTC3	ENST00000686240.1	n.*679+137C>T		intron_variant				ENSP00000508866.1
CRTC3	ENST00000691029.1	n.1266+137C>T		intron_variant				ENSP00000510507.1
CRTC3	ENST00000692149.1	n.*593+137C>T		intron_variant				ENSP00000510448.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18872 AN: 152096 Hom.: 1308 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.0754

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.108

GnomAD4 exome AF: 0.114 AC: 66160 AN: 581484 Hom.: 3980 AF XY: 0.114 AC XY: 34596 AN XY: 302660

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.0604

Gnomad4 ASJ exome AF: 0.0830

Gnomad4 EAS exome AF: 0.118

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.0982

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.113

GnomAD4 genome AF: 0.124 AC: 18871 AN: 152214 Hom.: 1303 Cov.: 32 AF XY: 0.123 AC XY: 9164 AN XY: 74422

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.0752

Gnomad4 ASJ AF: 0.0755

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.108

Alfa AF: 0.114 Hom.: 995

Bravo AF: 0.123

Asia WGS AF: 0.156 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.5
DANN	Benign	0.33

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: rs7495132; hg19: chr15-91172901;