chr19-18723314-C-T

Variant names:

• chr19-18723314-C-T
• rs2023878
• NM_015321.3:c.127-19596C>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.127-19596C>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 152,094 control chromosomes in the GnomAD database, including 4,933 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 (4933 hom., cov: 32)
• Consequence: CRTC1 NM_015321.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.822
• Publications: 17 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTC1	NM_015321.3	c.127-19596C>T		intron_variant	Intron 1 of 13	ENST00000321949.13	NP_056136.2
CRTC1	NM_001098482.2	c.127-19596C>T		intron_variant	Intron 1 of 14		NP_001091952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTC1	ENST00000321949.13	c.127-19596C>T		intron_variant	Intron 1 of 13	1	NM_015321.3	ENSP00000323332.7
CRTC1	ENST00000338797.10	c.127-19596C>T		intron_variant	Intron 1 of 14	1		ENSP00000345001.5

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36290 AN: 151976 Hom.: 4912 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.239 AC: 36333 AN: 152094 Hom.: 4933 Cov.: 32 AF XY: 0.246 AC XY: 18262 AN XY: 74356

African (AFR) AF: 0.255 AC: 10572 AN: 41490

American (AMR) AF: 0.300 AC: 4590 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 379 AN: 3470

East Asian (EAS) AF: 0.596 AC: 3071 AN: 5152

South Asian (SAS) AF: 0.291 AC: 1402 AN: 4820

European-Finnish (FIN) AF: 0.271 AC: 2871 AN: 10582

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

European-Non Finnish (NFE) AF: 0.187 AC: 12680 AN: 67984

Other (OTH) AF: 0.236 AC: 499 AN: 2114

Alfa AF: 0.208 Hom.: 12504

Bravo AF: 0.243

Asia WGS AF: 0.460 AC: 1595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.89
PhyloP100		-0.82
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: rs2023878; hg19: chr19-18834124;