rs140269231

Variant names:

• chr19-18753490-A-C
• NM_015321.3:c.539-10A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-18753490-A-C
• chr19-18753490-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015321.3(CRTC1):​c.539-10A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CRTC1 NM_015321.3 intron
• Scores: Splicing: ADA: 0.00001980
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTC1	NM_015321.3	c.539-10A>C		intron_variant	Intron 5 of 13	ENST00000321949.13	NP_056136.2
CRTC1	NM_001098482.2	c.587-10A>C		intron_variant	Intron 6 of 14		NP_001091952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTC1	ENST00000321949.13	c.539-10A>C		intron_variant	Intron 5 of 13	1	NM_015321.3	ENSP00000323332.7
CRTC1	ENST00000338797.10	c.587-10A>C		intron_variant	Intron 6 of 14	1		ENSP00000345001.5
CRTC1	ENST00000594658.5	c.416-10A>C		intron_variant	Intron 5 of 13	1		ENSP00000468893.1
CRTC1	ENST00000601916.1	c.314-10A>C		intron_variant	Intron 4 of 9	5		ENSP00000469285.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.50
DANN	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000020
dbscSNV1_RF	Benign	0.0060
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-18864300;