Variant chr15-90617932-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022769.5(CRTC3):c.663G>A(p.Pro221=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00449 in 1,612,776 control chromosomes in the GnomAD database, including 143 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0052 ( 10 hom., cov: 31)

Exomes 𝑓: 0.0044 ( 133 hom. )

Consequence

CRTC3
NM_022769.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.209

Variant links:

Genes affected

CRTC3 (HGNC:26148): (CREB regulated transcription coactivator 3) This gene is a member of the CREB regulated transcription coactivator gene family. This family regulates CREB-dependent gene transcription in a phosphorylation-independent manner and may be selective for cAMP-responsive genes. The protein encoded by this gene may induce mitochondrial biogenesis and attenuate catecholamine signaling in adipose tissue. A translocation event between this gene and Notch coactivator mastermind-like gene 2, which results in a fusion protein, has been reported in mucoepidermoid carcinomas. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

CRTC3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 15-90617932-G-A is Benign according to our data. Variant chr15-90617932-G-A is described in ClinVar as [Benign]. Clinvar id is 718782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.209 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRTC3	NM_022769.5 linkuse as main transcript	c.663G>A	p.Pro221=	synonymous_variant	8/15	ENST00000268184.11
CRTC3	NM_001042574.3 linkuse as main transcript	c.663G>A	p.Pro221=	synonymous_variant	8/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRTC3	ENST00000268184.11 linkuse as main transcript	c.663G>A	p.Pro221=	synonymous_variant	8/15	1	NM_022769.5	P3	Q6UUV7-1

Frequencies

GnomAD3 genomes

AF:

0.00524

AC:

796

AN:

151850

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00446

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.0436

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.0328

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00143

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00963

AC:

2420

AN:

251398

Hom.:

AF XY:

0.00891

AC XY:

1211

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.0147

Gnomad ASJ exome

AF:

0.00526

Gnomad EAS exome

AF:

0.0444

Gnomad SAS exome

AF:

0.00363

Gnomad FIN exome

AF:

0.0315

Gnomad NFE exome

AF:

0.00178

Gnomad OTH exome

AF:

0.00684

GnomAD4 exome

AF:

0.00441

AC:

6439

AN:

1460808

Hom.:

133

Cov.:

AF XY:

0.00435

AC XY:

3160

AN XY:

726808

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.0127

Gnomad4 ASJ exome

AF:

0.00628

Gnomad4 EAS exome

AF:

0.0690

Gnomad4 SAS exome

AF:

0.00397

Gnomad4 FIN exome

AF:

0.0310

Gnomad4 NFE exome

AF:

0.000627

Gnomad4 OTH exome

AF:

0.00426

GnomAD4 genome

AF:

0.00524

AC:

796

AN:

151968

Hom.:

Cov.:

AF XY:

0.00661

AC XY:

491

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00445

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.0435

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.0328

Gnomad4 NFE

AF:

0.00143

Gnomad4 OTH

AF:

0.00617

Alfa

AF:

0.00200

Hom.:

Bravo

AF:

0.00336

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 07, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over