rs117770608

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-18742927-C-A
• chr19-18742927-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_015321.3(CRTC1):​c.144C>A​(p.Ser48Ser) variant causes a synonymous 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. Synonymous variant affecting the same amino acid position (i.e. S48S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CRTC1 NM_015321.3 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP7: Synonymous conserved (PhyloP=-0.368 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTC1	NM_015321.3	c.144C>A	p.Ser48Ser	synonymous_variant	Exon 2 of 14	ENST00000321949.13	NP_056136.2
CRTC1	NM_001098482.2	c.144C>A	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>A	p.Ser48Ser	synonymous_variant	Exon 2 of 14	1	NM_015321.3	ENSP00000323332.7
CRTC1	ENST00000338797.10	c.144C>A	p.Ser48Ser	synonymous_variant	Exon 2 of 15	1		ENSP00000345001.5
CRTC1	ENST00000594658.5	c.21C>A	p.Ser7Ser	synonymous_variant	Exon 2 of 14	1		ENSP00000468893.1
CRTC1	ENST00000601916.1	c.-82C>A		5_prime_UTR_variant	Exon 1 of 10	5		ENSP00000469285.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250844 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	0.96
DANN	Benign	0.62
PhyloP100		-0.37
PromoterAI		0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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;