NM_015321.3:c.109C>G

Variant names:

• chr19-18683811-C-G
• rs1351838265
• NM_015321.3:c.109C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_015321.3(CRTC1):​c.109C>G​(p.Leu37Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000068 in 1,175,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: CRTC1 NM_015321.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06091082).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

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>G	p.Leu37Val	missense	Exon 1 of 14	NP_056136.2	Q6UUV9-1
	CRTC1	NM_001098482.2		c.109C>G	p.Leu37Val	missense	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>G	p.Leu37Val	missense	Exon 1 of 14	ENSP00000323332.7	Q6UUV9-1
	CRTC1	ENST00000338797.10	TSL:1	c.109C>G	p.Leu37Val	missense	Exon 1 of 15	ENSP00000345001.5	Q6UUV9-2
	CRTC1	ENST00000929718.1		c.109C>G	p.Leu37Val	missense	Exon 1 of 13	ENSP00000599777.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.00000680 AC: 8 AN: 1175850 Hom.: 0 Cov.: 32 AF XY: 0.00000518 AC XY: 3 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: 0.00 AC: 0 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: 0.00000637 AC: 6 AN: 941496

Other (OTH) AF: 0.0000458 AC: 2 AN: 43708

GnomAD4 genome Cov.: 27

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	22
DANN	Benign	0.86
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.56	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PhyloP100		2.0
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	0.17	N
REVEL	Benign	0.038
Sift	Benign	0.59	T
Sift4G	Benign	1.0	T
Polyphen		0.028	B
Vest4		0.13
MutPred		0.20		Gain of MoRF binding (P = 0.0818)
MVP		0.082
MPC		1.8
ClinPred		0.26	T
GERP RS		3.2
PromoterAI		0.018	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.11
gMVP		0.20
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs1351838265; hg19: chr19-18794621;