19-18742927-C-T

Variant names:

• chr19-18742927-C-T
• rs117770608
• NM_015321.3:c.144C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_015321.3(CRTC1):​c.144C>T​(p.Ser48Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000911 in 1,613,732 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00012 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000088 (0 hom.)
• Consequence: CRTC1 NM_015321.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.368
• 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 19-18742927-C-T is Benign according to our data. Variant chr19-18742927-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 751822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.368 with no splicing effect.
• BS2: High AC in GnomAd4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTC1	NM_015321.3	c.144C>T	p.Ser48Ser	synonymous_variant	Exon 2 of 14	ENST00000321949.13	NP_056136.2
CRTC1	NM_001098482.2	c.144C>T	p.Ser48Ser	synonymous_variant	Exon 2 of 15		NP_001091952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTC1	ENST00000321949.13	c.144C>T	p.Ser48Ser	synonymous_variant	Exon 2 of 14	1	NM_015321.3	ENSP00000323332.7
CRTC1	ENST00000338797.10	c.144C>T	p.Ser48Ser	synonymous_variant	Exon 2 of 15	1		ENSP00000345001.5
CRTC1	ENST00000594658.5	c.21C>T	p.Ser7Ser	synonymous_variant	Exon 2 of 14	1		ENSP00000468893.1
CRTC1	ENST00000601916.1	c.-82C>T		5_prime_UTR_variant	Exon 1 of 10	5		ENSP00000469285.1

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152232 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000116 AC: 29 AN: 250844 AF XY: 0.000111

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00103

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000529

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.0000883 AC: 129 AN: 1461382 Hom.: 0 Cov.: 31 AF XY: 0.000100 AC XY: 73 AN XY: 727050

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00214 AC: 85 AN: 39698

South Asian (SAS) AF: 0.0000928 AC: 8 AN: 86250

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53082

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1111886

Other (OTH) AF: 0.0000828 AC: 5 AN: 60378

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152350 Hom.: 1 Cov.: 33 AF XY: 0.000148 AC XY: 11 AN XY: 74488

African (AFR) AF: 0.00 AC: 0 AN: 41582

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68028

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000114 Hom.: 0

Bravo AF: 0.000110

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely 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	-0.37
CADD	Benign	0.78
DANN	Benign	0.65
PhyloP100		-0.37
PromoterAI		-0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs117770608; hg19: chr19-18853737;