chr15-90560454-C-T

Variant names:

• chr15-90560454-C-T
• rs17264145
• NM_022769.5:c.231+20317C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_022769.5(CRTC3):​c.231+20317C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 152,348 control chromosomes in the GnomAD database, including 43 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 0.019 (43 hom., cov: 32)
• Consequence: CRTC3 NM_022769.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.496
• 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=-0.56).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0192 (2932/152348) while in subpopulation NFE AF = 0.0298 (2029/68034). AF 95% confidence interval is 0.0287. There are 43 homozygotes in GnomAd4. There are 1464 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 43 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTC3	NM_022769.5	c.231+20317C>T		intron_variant	Intron 2 of 14	ENST00000268184.11	NP_073606.3
CRTC3	NM_001042574.3	c.231+20317C>T		intron_variant	Intron 2 of 14		NP_001036039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTC3	ENST00000268184.11	c.231+20317C>T		intron_variant	Intron 2 of 14	1	NM_022769.5	ENSP00000268184.6
CRTC3	ENST00000420329.6	c.231+20317C>T		intron_variant	Intron 2 of 14	2		ENSP00000416573.2
CRTC3	ENST00000686240.1	n.231+20317C>T		intron_variant	Intron 2 of 13			ENSP00000508866.1
CRTC3	ENST00000687075.1	n.54+20317C>T		intron_variant	Intron 1 of 8			ENSP00000510590.1
CRTC3	ENST00000691029.1	n.231+20317C>T		intron_variant	Intron 2 of 16			ENSP00000510507.1
CRTC3	ENST00000692149.1	n.231+20317C>T		intron_variant	Intron 2 of 12			ENSP00000510448.1

Frequencies

GnomAD3 genomes AF: 0.0193 AC: 2933 AN: 152230 Hom.: 43 Cov.: 32

Gnomad AFR AF: 0.00494

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00994

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0457

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0298

Gnomad OTH AF: 0.0138

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

GnomAD4 genome AF: 0.0192 AC: 2932 AN: 152348 Hom.: 43 Cov.: 32 AF XY: 0.0197 AC XY: 1464 AN XY: 74500

African (AFR) AF: 0.00493 AC: 205 AN: 41578

American (AMR) AF: 0.00993 AC: 152 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4828

European-Finnish (FIN) AF: 0.0457 AC: 485 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0298 AC: 2029 AN: 68034

Other (OTH) AF: 0.0137 AC: 29 AN: 2116

Alfa AF: 0.0263 Hom.: 81

Bravo AF: 0.0153

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		0.50
Mutation Taster		=100/0	polymorphism

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: rs17264145; hg19: chr15-91103686;