19-18736798-C-T

Position:

• chr19-18736798-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRTC1	NM_015321.3	c.127-6112C>T		intron_variant		ENST00000321949.13	NP_056136.2
CRTC1	NM_001098482.2	c.127-6112C>T		intron_variant			NP_001091952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRTC1	ENST00000321949.13	c.127-6112C>T		intron_variant		1	NM_015321.3	ENSP00000323332.7
CRTC1	ENST00000338797.10	c.127-6112C>T		intron_variant		1		ENSP00000345001.5
CRTC1	ENST00000594658.5	c.3+1155C>T		intron_variant		1		ENSP00000468893.1

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

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.212

Alfa AF: 0.157 Hom.: 729

Bravo AF: 0.218

Asia WGS AF: 0.266 AC: 925 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	6.0
DANN	Benign	0.70

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: rs6510997; hg19: chr19-18847608; COSMIC: COSV58717493;