NM_022769.5:c.1266+137C>T

Variant names:

• chr15-90629669-C-T
• rs7495132
• NM_022769.5:c.1266+137C>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.1266+137C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 733,698 control chromosomes in the GnomAD database, including 5,283 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 0.12 (1303 hom., cov: 32)
  • Exomes 𝑓: 0.11 (3980 hom.)
• Consequence: CRTC3 NM_022769.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.424
• Publications: 38 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]

CRTC3-AS1 (HGNC:51433): (CRTC3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTC3	NM_022769.5	c.1266+137C>T		intron_variant	Intron 11 of 14	ENST00000268184.11	NP_073606.3
CRTC3	NM_001042574.3	c.1266+137C>T		intron_variant	Intron 11 of 14		NP_001036039.1
CRTC3-AS1	NR_120372.1	n.510-9516G>A		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTC3	ENST00000268184.11	c.1266+137C>T		intron_variant	Intron 11 of 14	1	NM_022769.5	ENSP00000268184.6
CRTC3	ENST00000420329.6	c.1266+137C>T		intron_variant	Intron 11 of 14	2		ENSP00000416573.2
CRTC3	ENST00000686240.1	n.*679+137C>T		intron_variant	Intron 10 of 13			ENSP00000508866.1
CRTC3	ENST00000691029.1	n.1266+137C>T		intron_variant	Intron 11 of 16			ENSP00000510507.1
CRTC3	ENST00000692149.1	n.*593+137C>T		intron_variant	Intron 9 of 12			ENSP00000510448.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18872 AN: 152096 Hom.: 1308 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.0754

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.108

GnomAD4 exome AF: 0.114 AC: 66160 AN: 581484 Hom.: 3980 AF XY: 0.114 AC XY: 34596 AN XY: 302660

African (AFR) AF: 0.165 AC: 2486 AN: 15050

American (AMR) AF: 0.0604 AC: 1290 AN: 21346

Ashkenazi Jewish (ASJ) AF: 0.0830 AC: 1244 AN: 14994

East Asian (EAS) AF: 0.118 AC: 3784 AN: 32150

South Asian (SAS) AF: 0.142 AC: 7229 AN: 50824

European-Finnish (FIN) AF: 0.0982 AC: 3345 AN: 34076

Middle Eastern (MID) AF: 0.0624 AC: 161 AN: 2582

European-Non Finnish (NFE) AF: 0.114 AC: 43182 AN: 379932

Other (OTH) AF: 0.113 AC: 3439 AN: 30530

GnomAD4 genome AF: 0.124 AC: 18871 AN: 152214 Hom.: 1303 Cov.: 32 AF XY: 0.123 AC XY: 9164 AN XY: 74422

African (AFR) AF: 0.163 AC: 6774 AN: 41502

American (AMR) AF: 0.0752 AC: 1151 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0755 AC: 262 AN: 3472

East Asian (EAS) AF: 0.187 AC: 968 AN: 5180

South Asian (SAS) AF: 0.159 AC: 768 AN: 4828

European-Finnish (FIN) AF: 0.103 AC: 1090 AN: 10588

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7561 AN: 68018

Other (OTH) AF: 0.108 AC: 229 AN: 2116

Alfa AF: 0.115 Hom.: 2705

Bravo AF: 0.123

Asia WGS AF: 0.156 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.5
DANN	Benign	0.33
PhyloP100		0.42
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: rs7495132; hg19: chr15-91172901;