15-90596819-C-T

Variant names:

• chr15-90596819-C-T
• rs8028854
• NM_022769.5:c.351+3064C>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.351+3064C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 152,088 control chromosomes in the GnomAD database, including 35,437 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 (35437 hom., cov: 33)
• Consequence: CRTC3 NM_022769.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.694
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTC3	NM_022769.5	c.351+3064C>T		intron_variant	Intron 3 of 14	ENST00000268184.11	NP_073606.3
CRTC3	NM_001042574.3	c.351+3064C>T		intron_variant	Intron 3 of 14		NP_001036039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTC3	ENST00000268184.11	c.351+3064C>T		intron_variant	Intron 3 of 14	1	NM_022769.5	ENSP00000268184.6
CRTC3	ENST00000420329.6	c.351+3064C>T		intron_variant	Intron 3 of 14	2		ENSP00000416573.2
CRTC3	ENST00000558005.1	c.42+3064C>T		intron_variant	Intron 1 of 6	4		ENSP00000452676.1
CRTC3	ENST00000686240.1	n.351+3064C>T		intron_variant	Intron 3 of 13			ENSP00000508866.1
CRTC3	ENST00000687075.1	n.174+3064C>T		intron_variant	Intron 2 of 8			ENSP00000510590.1
CRTC3	ENST00000691029.1	n.351+3064C>T		intron_variant	Intron 3 of 16			ENSP00000510507.1
CRTC3	ENST00000692149.1	n.351+3064C>T		intron_variant	Intron 3 of 12			ENSP00000510448.1

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101924 AN: 151970 Hom.: 35423 Cov.: 33

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.710

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

GnomAD4 genome AF: 0.670 AC: 101972 AN: 152088 Hom.: 35437 Cov.: 33 AF XY: 0.668 AC XY: 49705 AN XY: 74358

African (AFR) AF: 0.483 AC: 20006 AN: 41436

American (AMR) AF: 0.663 AC: 10127 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 2652 AN: 3472

East Asian (EAS) AF: 0.615 AC: 3184 AN: 5176

South Asian (SAS) AF: 0.730 AC: 3517 AN: 4816

European-Finnish (FIN) AF: 0.734 AC: 7765 AN: 10580

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.768 AC: 52235 AN: 68000

Other (OTH) AF: 0.711 AC: 1504 AN: 2116

Alfa AF: 0.736 Hom.: 88361

Bravo AF: 0.656

Asia WGS AF: 0.651 AC: 2268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.59
DANN	Benign	0.18
PhyloP100		-0.69
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: rs8028854; hg19: chr15-91140051;