rs12462498

Variant names:

• chr19-18722140-C-T
• rs12462498
• NM_015321.3:c.127-20770C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015321.3(CRTC1):​c.127-20770C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,224 control chromosomes in the GnomAD database, including 4,929 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 0.24 (4929 hom., cov: 33)
• Consequence: CRTC1 NM_015321.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242
• Publications: 6 publications found

Genes affected

CRTC1 (HGNC:16062): (CREB regulated transcription coactivator 1) Enables cAMP response element binding protein binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in cytosol; nuclear body; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015321.3. 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
	CRTC1	NM_015321.3	MANE Select	c.127-20770C>T		intron	N/A	NP_056136.2	Q6UUV9-1
	CRTC1	NM_001098482.2		c.127-20770C>T		intron	N/A	NP_001091952.1	Q6UUV9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTC1	ENST00000321949.13	TSL:1 MANE Select	c.127-20770C>T		intron	N/A	ENSP00000323332.7	Q6UUV9-1
	CRTC1	ENST00000338797.10	TSL:1	c.127-20770C>T		intron	N/A	ENSP00000345001.5	Q6UUV9-2
	CRTC1	ENST00000929718.1		c.127-20770C>T		intron	N/A	ENSP00000599777.1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36305 AN: 152106 Hom.: 4908 Cov.: 33

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.239 AC: 36348 AN: 152224 Hom.: 4929 Cov.: 33 AF XY: 0.245 AC XY: 18265 AN XY: 74420

African (AFR) AF: 0.255 AC: 10578 AN: 41540

American (AMR) AF: 0.302 AC: 4612 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 374 AN: 3470

East Asian (EAS) AF: 0.595 AC: 3084 AN: 5180

South Asian (SAS) AF: 0.290 AC: 1401 AN: 4826

European-Finnish (FIN) AF: 0.271 AC: 2869 AN: 10592

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12666 AN: 68010

Other (OTH) AF: 0.235 AC: 497 AN: 2112

Alfa AF: 0.219 Hom.: 843

Bravo AF: 0.244

Asia WGS AF: 0.460 AC: 1595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.88
DANN	Benign	0.75
PhyloP100		-0.24
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: rs12462498; hg19: chr19-18832950;