chr15-90642762-C-T

Variant names:

• chr15-90642762-C-T
• rs3743401
• NM_022769.5:c.*622C>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.*622C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 231,372 control chromosomes in the GnomAD database, including 11,990 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 0.32 (9009 hom., cov: 32)
  • Exomes 𝑓: 0.26 (2981 hom.)
• Consequence: CRTC3 NM_022769.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.500
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022769.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTC3	NM_022769.5	MANE Select	c.*622C>T		3_prime_UTR	Exon 15 of 15	NP_073606.3
	CRTC3	NM_001042574.3		c.*622C>T		3_prime_UTR	Exon 15 of 15	NP_001036039.1
	CRTC3-AS1	NR_120372.1		n.294-1505G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTC3	ENST00000268184.11	TSL:1 MANE Select	c.*622C>T		3_prime_UTR	Exon 15 of 15	ENSP00000268184.6
	CRTC3	ENST00000420329.6	TSL:2	c.*622C>T		3_prime_UTR	Exon 15 of 15	ENSP00000416573.2
	CRTC3	ENST00000686240.1		n.*1895C>T		non_coding_transcript_exon	Exon 14 of 14	ENSP00000508866.1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49291 AN: 152084 Hom.: 8996 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.296

GnomAD4 exome AF: 0.264 AC: 20933 AN: 79170 Hom.: 2981 Cov.: 0 AF XY: 0.259 AC XY: 9480 AN XY: 36560

African (AFR) AF: 0.490 AC: 1809 AN: 3690

American (AMR) AF: 0.332 AC: 829 AN: 2496

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 1211 AN: 4920

East Asian (EAS) AF: 0.325 AC: 3594 AN: 11072

South Asian (SAS) AF: 0.206 AC: 147 AN: 714

European-Finnish (FIN) AF: 0.249 AC: 101 AN: 406

Middle Eastern (MID) AF: 0.212 AC: 102 AN: 482

European-Non Finnish (NFE) AF: 0.233 AC: 11377 AN: 48840

Other (OTH) AF: 0.269 AC: 1763 AN: 6550

GnomAD4 genome AF: 0.324 AC: 49346 AN: 152202 Hom.: 9009 Cov.: 32 AF XY: 0.326 AC XY: 24275 AN XY: 74424

African (AFR) AF: 0.497 AC: 20645 AN: 41526

American (AMR) AF: 0.336 AC: 5148 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 821 AN: 3470

East Asian (EAS) AF: 0.329 AC: 1702 AN: 5176

South Asian (SAS) AF: 0.213 AC: 1027 AN: 4828

European-Finnish (FIN) AF: 0.281 AC: 2974 AN: 10596

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16182 AN: 67992

Other (OTH) AF: 0.295 AC: 622 AN: 2112

Alfa AF: 0.269 Hom.: 17352

Bravo AF: 0.338

Asia WGS AF: 0.298 AC: 1032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.67
PhyloP100		-0.50
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: rs3743401; hg19: chr15-91185994; COSMIC: COSV51598684; COSMIC: COSV51598684;