Variant 19-18753490-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015321.3(CRTC1):c.539-10A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,594,552 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 11 hom., cov: 31)

Exomes 𝑓: 0.00075 ( 17 hom. )

Consequence

CRTC1
NM_015321.3 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00004676

Clinical Significance

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

Conservation

PhyloP100: -2.29

Variant links:

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]

CRTC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 19-18753490-A-G is Benign according to our data. Variant chr19-18753490-A-G is described in ClinVar as [Benign]. Clinvar id is 788814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00733 (1108/151062) while in subpopulation AFR AF= 0.0258 (1060/41034). AF 95% confidence interval is 0.0245. There are 11 homozygotes in gnomad4. There are 520 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1108 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRTC1	NM_015321.3 linkuse as main transcript	c.539-10A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000321949.13	NP_056136.2
CRTC1	NM_001098482.2 linkuse as main transcript	c.587-10A>G		splice_polypyrimidine_tract_variant, intron_variant			NP_001091952.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
CRTC1	ENST00000321949.13 linkuse as main transcript	c.539-10A>G	splice_polypyrimidine_tract_variant, intron_variant	1	NM_015321.3	ENSP00000323332	A1	Q6UUV9-1
CRTC1	ENST00000338797.10 linkuse as main transcript	c.587-10A>G	splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000345001	P4	Q6UUV9-2
CRTC1	ENST00000594658.5 linkuse as main transcript	c.416-10A>G	splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000468893
CRTC1	ENST00000601916.1 linkuse as main transcript	c.314-10A>G	splice_polypyrimidine_tract_variant, intron_variant	5		ENSP00000469285

Frequencies

GnomAD3 genomes

AF:

0.00734

AC:

1108

AN:

150942

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0259

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00238

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:

0.0000737

Gnomad OTH

AF:

0.00339

GnomAD3 exomes

AF:

0.00182

AC:

434

AN:

238692

Hom.:

AF XY:

0.00121

AC XY:

156

AN XY:

129096

show subpopulations

Gnomad AFR exome

AF:

0.0252

Gnomad AMR exome

AF:

0.000744

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000363

Gnomad OTH exome

AF:

0.000859

GnomAD4 exome

AF:

0.000752

AC:

1085

AN:

1443490

Hom.:

Cov.:

AF XY:

0.000629

AC XY:

452

AN XY:

718388

show subpopulations

Gnomad4 AFR exome

AF:

0.0272

Gnomad4 AMR exome

AF:

0.00111

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000717

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000236

Gnomad4 OTH exome

AF:

0.00196

GnomAD4 genome

AF:

0.00733

AC:

1108

AN:

151062

Hom.:

Cov.:

AF XY:

0.00706

AC XY:

520

AN XY:

73696

show subpopulations

Gnomad4 AFR

AF:

0.0258

Gnomad4 AMR

AF:

0.00238

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000737

Gnomad4 OTH

AF:

0.00335

Alfa

AF:

0.00512

Hom.:

Bravo

AF:

0.00849

Asia WGS

AF:

0.00115

AC:

AN:

3478

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 08, 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

-0.85

CADD

Benign

0.32

DANN

Benign

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000047

dbscSNV1_RF

Benign

0.010

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

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