chr1-153947810-G-A

Position:

• chr1-153947810-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181715.3(CRTC2):​c.*299C>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 0.295 in 434,464 control chromosomes in the GnomAD database, including 20,345 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 0.27 (6101 hom., cov: 32)
  • Exomes 𝑓: 0.31 (14244 hom.)
• Consequence: CRTC2 NM_181715.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45

Genes affected

CRTC2 (HGNC:27301): (CREB regulated transcription coactivator 2) This gene encodes a member of the transducers of regulated cAMP response element-binding protein activity family of transcription coactivators. These proteins promote the transcription of genes targeted by the cAMP response element-binding protein, and therefore play an important role in many cellular processes. Under basal conditions the encoded protein is phosphorylated by AMP-activated protein kinase or the salt-inducible kinases and is sequestered in the cytoplasm. Upon activation by elevated cAMP or calcium, the encoded protein translocates to the nucleus and increases target gene expression. Single nucleotide polymorphisms in this gene may increase the risk of type 2 diabetes. A pseudogene of this gene is located on the long arm of chromosome 5. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRTC2	NM_181715.3	c.*299C>T		3_prime_UTR_variant	14/14	ENST00000368633.2	NP_859066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRTC2	ENST00000368633.2	c.*299C>T		3_prime_UTR_variant	14/14	1	NM_181715.3	ENSP00000357622	P1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41003 AN: 151900 Hom.: 6101 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.298

GnomAD4 exome AF: 0.309 AC: 87199 AN: 282448 Hom.: 14244 Cov.: 0 AF XY: 0.310 AC XY: 46374 AN XY: 149526

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.398

Gnomad4 ASJ exome AF: 0.304

Gnomad4 EAS exome AF: 0.293

Gnomad4 SAS exome AF: 0.320

Gnomad4 FIN exome AF: 0.339

Gnomad4 NFE exome AF: 0.309

Gnomad4 OTH exome AF: 0.302

GnomAD4 genome AF: 0.270 AC: 41030 AN: 152016 Hom.: 6101 Cov.: 32 AF XY: 0.275 AC XY: 20438 AN XY: 74290

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.295

Alfa AF: 0.307 Hom.: 6437

Bravo AF: 0.270

Asia WGS AF: 0.284 AC: 990 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	9.2
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs8450; hg19: chr1-153920286;