19-18747094-C-T

Variant names:

• chr19-18747094-C-T
• rs777137375
• NM_015321.3:c.423C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_015321.3(CRTC1):​c.423C>T​(p.Pro141Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000422 in 1,612,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000042 (0 hom.)
• Consequence: CRTC1 NM_015321.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.37
• Publications: 0 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 19-18747094-C-T is Benign according to our data. Variant chr19-18747094-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 753883.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.37 with no splicing effect.
• BS2: High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTC1	NM_015321.3	c.423C>T	p.Pro141Pro	synonymous_variant	Exon 4 of 14	ENST00000321949.13	NP_056136.2
CRTC1	NM_001098482.2	c.471C>T	p.Pro157Pro	synonymous_variant	Exon 5 of 15		NP_001091952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTC1	ENST00000321949.13	c.423C>T	p.Pro141Pro	synonymous_variant	Exon 4 of 14	1	NM_015321.3	ENSP00000323332.7
CRTC1	ENST00000338797.10	c.471C>T	p.Pro157Pro	synonymous_variant	Exon 5 of 15	1		ENSP00000345001.5
CRTC1	ENST00000594658.5	c.300C>T	p.Pro100Pro	synonymous_variant	Exon 4 of 14	1		ENSP00000468893.1
CRTC1	ENST00000601916.1	c.198C>T	p.Pro66Pro	synonymous_variant	Exon 3 of 10	5		ENSP00000469285.1

Frequencies

GnomAD3 genomes AF: 0.0000463 AC: 7 AN: 151238 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000487

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000659

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000442

Gnomad OTH AF: 0.000481

GnomAD2 exomes AF: 0.0000440 AC: 11 AN: 250156 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000418 AC: 61 AN: 1460932 Hom.: 0 Cov.: 32 AF XY: 0.0000358 AC XY: 26 AN XY: 726812

African (AFR) AF: 0.0000897 AC: 3 AN: 33428

American (AMR) AF: 0.000134 AC: 6 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.00 AC: 0 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.0000342 AC: 38 AN: 1111540

Other (OTH) AF: 0.000232 AC: 14 AN: 60358

GnomAD4 genome AF: 0.0000463 AC: 7 AN: 151238 Hom.: 0 Cov.: 30 AF XY: 0.0000677 AC XY: 5 AN XY: 73868

African (AFR) AF: 0.0000487 AC: 2 AN: 41034

American (AMR) AF: 0.0000659 AC: 1 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5134

South Asian (SAS) AF: 0.00 AC: 0 AN: 4792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000442 AC: 3 AN: 67834

Other (OTH) AF: 0.000481 AC: 1 AN: 2080

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000113

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 22, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	5.5
DANN	Benign	0.63
PhyloP100		-4.4
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs777137375; hg19: chr19-18857904;