15-90539300-A-G

Variant names:

• chr15-90539300-A-G
• rs3862435
• NM_022769.5:c.133-739A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022769.5(CRTC3):​c.133-739A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,244 control chromosomes in the GnomAD database, including 60,460 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 0.89 (60460 hom., cov: 32)
• Consequence: CRTC3 NM_022769.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTC3	NM_022769.5	c.133-739A>G		intron_variant	Intron 1 of 14	ENST00000268184.11	NP_073606.3
CRTC3	NM_001042574.3	c.133-739A>G		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.133-739A>G		intron_variant	Intron 1 of 14	1	NM_022769.5	ENSP00000268184.6
CRTC3	ENST00000420329.6	c.133-739A>G		intron_variant	Intron 1 of 14	2		ENSP00000416573.2
CRTC3	ENST00000686240.1	n.133-739A>G		intron_variant	Intron 1 of 13			ENSP00000508866.1
CRTC3	ENST00000691029.1	n.133-739A>G		intron_variant	Intron 1 of 16			ENSP00000510507.1
CRTC3	ENST00000692149.1	n.133-739A>G		intron_variant	Intron 1 of 12			ENSP00000510448.1

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135374 AN: 152126 Hom.: 60414 Cov.: 32

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.955

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.906

Gnomad OTH AF: 0.900

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

GnomAD4 genome AF: 0.890 AC: 135472 AN: 152244 Hom.: 60460 Cov.: 32 AF XY: 0.887 AC XY: 66015 AN XY: 74440

African (AFR) AF: 0.900 AC: 37399 AN: 41542

American (AMR) AF: 0.833 AC: 12731 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.937 AC: 3254 AN: 3472

East Asian (EAS) AF: 0.776 AC: 4014 AN: 5174

South Asian (SAS) AF: 0.776 AC: 3745 AN: 4828

European-Finnish (FIN) AF: 0.910 AC: 9654 AN: 10604

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.906 AC: 61634 AN: 68016

Other (OTH) AF: 0.899 AC: 1901 AN: 2114

Alfa AF: 0.897 Hom.: 31433

Bravo AF: 0.887

Asia WGS AF: 0.783 AC: 2720 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.1
DANN	Benign	0.65
PhyloP100		0.029
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: rs3862435; hg19: chr15-91082532;