chr15-90585876-C-T

Variant names:

• chr15-90585876-C-T
• rs6496696
• NM_022769.5:c.232-7760C>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.232-7760C>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
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022769.5. 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
	CRTC3	NM_022769.5	MANE Select	c.232-7760C>T		intron	N/A	NP_073606.3	Q6UUV7-1
	CRTC3	NM_001042574.3		c.232-7760C>T		intron	N/A	NP_001036039.1	Q6UUV7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTC3	ENST00000268184.11	TSL:1 MANE Select	c.232-7760C>T		intron	N/A	ENSP00000268184.6	Q6UUV7-1
	CRTC3	ENST00000420329.6	TSL:2	c.232-7760C>T		intron	N/A	ENSP00000416573.2	Q6UUV7-3
	CRTC3	ENST00000560098.5	TSL:1	c.232-12574C>T		intron	N/A	ENSP00000452640.1	H0YK33

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

African (AFR) AF: 0.645 AC: 26756 AN: 41484

American (AMR) AF: 0.617 AC: 9425 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 2495 AN: 3468

East Asian (EAS) AF: 0.769 AC: 3974 AN: 5166

South Asian (SAS) AF: 0.841 AC: 4053 AN: 4822

European-Finnish (FIN) AF: 0.661 AC: 6976 AN: 10556

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.681 AC: 46263 AN: 67974

Other (OTH) AF: 0.680 AC: 1438 AN: 2114

Alfa AF: 0.681 Hom.: 153074

Bravo AF: 0.662

Asia WGS AF: 0.781 AC: 2719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.5
DANN	Benign	0.50
PhyloP100		-0.055
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: rs6496696; hg19: chr15-91129108;