rs3862434

Variant names:

• chr15-90537155-A-G
• rs3862434
• NM_022769.5:c.133-2884A>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.133-2884A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,988 control chromosomes in the GnomAD database, including 18,132 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 0.48 (18132 hom., cov: 32)
• Consequence: CRTC3 NM_022769.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.770
• 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]

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 (NFE) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTC3	NM_022769.5	c.133-2884A>G		intron_variant	Intron 1 of 14	ENST00000268184.11	NP_073606.3
CRTC3	NM_001042574.3	c.133-2884A>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.133-2884A>G		intron_variant	Intron 1 of 14	1	NM_022769.5	ENSP00000268184.6
CRTC3	ENST00000420329.6	c.133-2884A>G		intron_variant	Intron 1 of 14	2		ENSP00000416573.2
CRTC3	ENST00000686240.1	n.133-2884A>G		intron_variant	Intron 1 of 13			ENSP00000508866.1
CRTC3	ENST00000691029.1	n.133-2884A>G		intron_variant	Intron 1 of 16			ENSP00000510507.1
CRTC3	ENST00000692149.1	n.133-2884A>G		intron_variant	Intron 1 of 12			ENSP00000510448.1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72769 AN: 151870 Hom.: 18114 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.479 AC: 72818 AN: 151988 Hom.: 18132 Cov.: 32 AF XY: 0.477 AC XY: 35401 AN XY: 74284

African (AFR) AF: 0.409 AC: 16925 AN: 41418

American (AMR) AF: 0.408 AC: 6233 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2079 AN: 3468

East Asian (EAS) AF: 0.169 AC: 877 AN: 5182

South Asian (SAS) AF: 0.391 AC: 1882 AN: 4818

European-Finnish (FIN) AF: 0.551 AC: 5803 AN: 10528

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.550 AC: 37394 AN: 67994

Other (OTH) AF: 0.488 AC: 1028 AN: 2106

Alfa AF: 0.492 Hom.: 6817

Bravo AF: 0.460

Asia WGS AF: 0.306 AC: 1062 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	0.20
DANN	Benign	0.75
PhyloP100		-0.77
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: rs3862434; hg19: chr15-91080387;