19-18760188-G-A

Variant names:

• chr19-18760188-G-A
• rs112538945
• NM_015321.3:c.846G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_015321.3(CRTC1):​c.846G>A​(p.Ala282Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,612,908 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0057 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (26 hom.)
• Consequence: CRTC1 NM_015321.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.97
• Publications: 1 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 19-18760188-G-A is Benign according to our data. Variant chr19-18760188-G-A is described in ClinVar as [Benign]. Clinvar id is 788467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.97 with no splicing effect.
• BS2: High AC in GnomAd4 at 868 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTC1	NM_015321.3	c.846G>A	p.Ala282Ala	synonymous_variant	Exon 8 of 14	ENST00000321949.13	NP_056136.2
CRTC1	NM_001098482.2	c.894G>A	p.Ala298Ala	synonymous_variant	Exon 9 of 15		NP_001091952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTC1	ENST00000321949.13	c.846G>A	p.Ala282Ala	synonymous_variant	Exon 8 of 14	1	NM_015321.3	ENSP00000323332.7
CRTC1	ENST00000338797.10	c.894G>A	p.Ala298Ala	synonymous_variant	Exon 9 of 15	1		ENSP00000345001.5
CRTC1	ENST00000594658.5	c.723G>A	p.Ala241Ala	synonymous_variant	Exon 8 of 14	1		ENSP00000468893.1
CRTC1	ENST00000601916.1	c.621G>A	p.Ala207Ala	synonymous_variant	Exon 7 of 10	5		ENSP00000469285.1

Frequencies

GnomAD3 genomes AF: 0.00569 AC: 866 AN: 152134 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0157

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00346 AC: 845 AN: 244182 AF XY: 0.00367

Gnomad AFR exome AF: 0.0156

Gnomad AMR exome AF: 0.00102

Gnomad ASJ exome AF: 0.0165

Gnomad EAS exome AF: 0.000110

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000303

Gnomad OTH exome AF: 0.00251

GnomAD4 exome AF: 0.00164 AC: 2392 AN: 1460656 Hom.: 26 Cov.: 33 AF XY: 0.00196 AC XY: 1425 AN XY: 726658

African (AFR) AF: 0.0157 AC: 525 AN: 33454

American (AMR) AF: 0.00103 AC: 46 AN: 44572

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 407 AN: 26076

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39676

South Asian (SAS) AF: 0.0122 AC: 1049 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53062

Middle Eastern (MID) AF: 0.00416 AC: 24 AN: 5768

European-Non Finnish (NFE) AF: 0.000136 AC: 151 AN: 1111518

Other (OTH) AF: 0.00312 AC: 188 AN: 60316

GnomAD4 genome AF: 0.00570 AC: 868 AN: 152252 Hom.: 8 Cov.: 32 AF XY: 0.00574 AC XY: 427 AN XY: 74438

African (AFR) AF: 0.0159 AC: 660 AN: 41540

American (AMR) AF: 0.00268 AC: 41 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 55 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5174

South Asian (SAS) AF: 0.0157 AC: 76 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68012

Other (OTH) AF: 0.00568 AC: 12 AN: 2112

Alfa AF: 0.00328 Hom.: 3

Bravo AF: 0.00567

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.8
DANN	Benign	0.87
PhyloP100		-4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs112538945; hg19: chr19-18870998;