19-18736798-C-T

Variant names:

• chr19-18736798-C-T
• rs6510997
• NM_015321.3:c.127-6112C>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.127-6112C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 151,988 control chromosomes in the GnomAD database, including 3,598 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 0.21 (3598 hom., cov: 33)
• Consequence: CRTC1 NM_015321.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243
• Publications: 10 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 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.127-6112C>T		intron	N/A	NP_056136.2	Q6UUV9-1
	CRTC1	NM_001098482.2		c.127-6112C>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.127-6112C>T		intron	N/A	ENSP00000323332.7	Q6UUV9-1
	CRTC1	ENST00000338797.10	TSL:1	c.127-6112C>T		intron	N/A	ENSP00000345001.5	Q6UUV9-2
	CRTC1	ENST00000594658.5	TSL:1	c.3+1155C>T		intron	N/A	ENSP00000468893.1	M0QX46

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32118 AN: 151872 Hom.: 3588 Cov.: 33

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.212 AC: 32161 AN: 151988 Hom.: 3598 Cov.: 33 AF XY: 0.211 AC XY: 15675 AN XY: 74332

African (AFR) AF: 0.254 AC: 10498 AN: 41338

American (AMR) AF: 0.190 AC: 2899 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 792 AN: 3472

East Asian (EAS) AF: 0.296 AC: 1526 AN: 5160

South Asian (SAS) AF: 0.232 AC: 1122 AN: 4830

European-Finnish (FIN) AF: 0.136 AC: 1444 AN: 10618

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13183 AN: 67960

Other (OTH) AF: 0.212 AC: 448 AN: 2116

Alfa AF: 0.167 Hom.: 997

Bravo AF: 0.218

Asia WGS AF: 0.266 AC: 925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.0
DANN	Benign	0.70
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: rs6510997; hg19: chr19-18847608; COSMIC: COSV58717493;