15-90531821-C-T

Variant names:

• chr15-90531821-C-T
• rs3862432
• NM_022769.5:c.132+1618C>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.132+1618C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 151,996 control chromosomes in the GnomAD database, including 35,000 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 (35000 hom., cov: 32)
• Consequence: CRTC3 NM_022769.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210
• Publications: 6 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTC3	NM_022769.5	c.132+1618C>T		intron_variant	Intron 1 of 14	ENST00000268184.11	NP_073606.3
CRTC3	NM_001042574.3	c.132+1618C>T		intron_variant	Intron 1 of 14		NP_001036039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTC3	ENST00000268184.11	c.132+1618C>T		intron_variant	Intron 1 of 14	1	NM_022769.5	ENSP00000268184.6
CRTC3	ENST00000420329.6	c.132+1618C>T		intron_variant	Intron 1 of 14	2		ENSP00000416573.2
CRTC3	ENST00000686240.1	n.132+1618C>T		intron_variant	Intron 1 of 13			ENSP00000508866.1
CRTC3	ENST00000691029.1	n.132+1618C>T		intron_variant	Intron 1 of 16			ENSP00000510507.1
CRTC3	ENST00000692149.1	n.132+1618C>T		intron_variant	Intron 1 of 12			ENSP00000510448.1

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101479 AN: 151878 Hom.: 34977 Cov.: 32

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.695

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

GnomAD4 genome AF: 0.668 AC: 101540 AN: 151996 Hom.: 35000 Cov.: 32 AF XY: 0.671 AC XY: 49825 AN XY: 74300

African (AFR) AF: 0.491 AC: 20303 AN: 41388

American (AMR) AF: 0.644 AC: 9827 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 2845 AN: 3468

East Asian (EAS) AF: 0.621 AC: 3215 AN: 5174

South Asian (SAS) AF: 0.676 AC: 3256 AN: 4818

European-Finnish (FIN) AF: 0.788 AC: 8328 AN: 10568

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.757 AC: 51440 AN: 67996

Other (OTH) AF: 0.697 AC: 1472 AN: 2112

Alfa AF: 0.729 Hom.: 77784

Bravo AF: 0.647

Asia WGS AF: 0.645 AC: 2243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.9
DANN	Benign	0.51
PhyloP100		0.21
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: rs3862432; hg19: chr15-91075053; COSMIC: COSV107270149;