19-18683811-C-T

Variant names:

• chr19-18683811-C-T
• rs1351838265
• NM_015321.3:c.109C>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.109C>T​(p.Leu37Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000151 in 1,322,248 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000068 (0 hom., cov: 27)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: CRTC1 NM_015321.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• 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=-0.3).
• BP7: Synonymous conserved (PhyloP=1.99 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015321.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTC1	NM_015321.3	MANE Select	c.109C>T	p.Leu37Leu	synonymous	Exon 1 of 14	NP_056136.2	Q6UUV9-1
	CRTC1	NM_001098482.2		c.109C>T	p.Leu37Leu	synonymous	Exon 1 of 15	NP_001091952.1	Q6UUV9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTC1	ENST00000321949.13	TSL:1 MANE Select	c.109C>T	p.Leu37Leu	synonymous	Exon 1 of 14	ENSP00000323332.7	Q6UUV9-1
	CRTC1	ENST00000338797.10	TSL:1	c.109C>T	p.Leu37Leu	synonymous	Exon 1 of 15	ENSP00000345001.5	Q6UUV9-2
	CRTC1	ENST00000929718.1		c.109C>T	p.Leu37Leu	synonymous	Exon 1 of 13	ENSP00000599777.1

Frequencies

GnomAD3 genomes AF: 0.00000683 AC: 1 AN: 146398 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 8.50e-7 AC: 1 AN: 1175850 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 578878

African (AFR) AF: 0.00 AC: 0 AN: 22956

American (AMR) AF: 0.00 AC: 0 AN: 24608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17690

East Asian (EAS) AF: 0.00 AC: 0 AN: 20130

South Asian (SAS) AF: 0.0000155 AC: 1 AN: 64328

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4618

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 941496

Other (OTH) AF: 0.00 AC: 0 AN: 43708

GnomAD4 genome AF: 0.00000683 AC: 1 AN: 146398 Hom.: 0 Cov.: 27 AF XY: 0.0000140 AC XY: 1 AN XY: 71266

African (AFR) AF: 0.0000248 AC: 1 AN: 40356

American (AMR) AF: 0.00 AC: 0 AN: 14760

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3398

East Asian (EAS) AF: 0.00 AC: 0 AN: 4996

South Asian (SAS) AF: 0.00 AC: 0 AN: 4736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8816

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66120

Other (OTH) AF: 0.00 AC: 0 AN: 2012

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	15
DANN	Benign	0.97
PhyloP100		2.0
PromoterAI		-0.035	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1351838265; hg19: chr19-18794621;