rs8450

Variant names:

• chr1-153947810-G-A
• rs8450
• NM_181715.3:c.*299C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-153947810-G-A
• chr1-153947810-G-C
• chr1-153947810-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181715.3. 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
	CRTC2	NM_181715.3	MANE Select	c.*299C>T		3_prime_UTR	Exon 14 of 14	NP_859066.1	Q53ET0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTC2	ENST00000368633.2	TSL:1 MANE Select	c.*299C>T		3_prime_UTR	Exon 14 of 14	ENSP00000357622.1	Q53ET0
	CRTC2	ENST00000461638.6	TSL:1	n.*762C>T		non_coding_transcript_exon	Exon 13 of 13	ENSP00000434115.2	H0YDQ8
	CRTC2	ENST00000461638.6	TSL:1	n.*762C>T		3_prime_UTR	Exon 13 of 13	ENSP00000434115.2	H0YDQ8

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

African (AFR) AF: 0.128 AC: 1114 AN: 8724

American (AMR) AF: 0.398 AC: 4817 AN: 12096

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 2642 AN: 8700

East Asian (EAS) AF: 0.293 AC: 4796 AN: 16388

South Asian (SAS) AF: 0.320 AC: 12084 AN: 37722

European-Finnish (FIN) AF: 0.339 AC: 4857 AN: 14312

Middle Eastern (MID) AF: 0.354 AC: 427 AN: 1206

European-Non Finnish (NFE) AF: 0.309 AC: 51649 AN: 167342

Other (OTH) AF: 0.302 AC: 4813 AN: 15958

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

African (AFR) AF: 0.138 AC: 5717 AN: 41476

American (AMR) AF: 0.384 AC: 5856 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1039 AN: 3470

East Asian (EAS) AF: 0.284 AC: 1469 AN: 5172

South Asian (SAS) AF: 0.329 AC: 1580 AN: 4806

European-Finnish (FIN) AF: 0.341 AC: 3602 AN: 10570

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20849 AN: 67948

Other (OTH) AF: 0.295 AC: 620 AN: 2102

Alfa AF: 0.305 Hom.: 7702

Bravo AF: 0.270

Asia WGS AF: 0.284 AC: 990 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	9.2
DANN	Benign	0.75
PhyloP100		1.5
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: rs8450; hg19: chr1-153920286;