rs1177950459

Variant names:

• chr19-18747056-G-A
• rs1177950459
• NM_015321.3:c.385G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-18747056-G-A
• chr19-18747056-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015321.3(CRTC1):​c.385G>A​(p.Asp129Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,076 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CRTC1 NM_015321.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.24
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.385G>A	p.Asp129Asn	missense	Exon 4 of 14	NP_056136.2	Q6UUV9-1
	CRTC1	NM_001098482.2		c.433G>A	p.Asp145Asn	missense	Exon 5 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.385G>A	p.Asp129Asn	missense	Exon 4 of 14	ENSP00000323332.7	Q6UUV9-1
	CRTC1	ENST00000338797.10	TSL:1	c.433G>A	p.Asp145Asn	missense	Exon 5 of 15	ENSP00000345001.5	Q6UUV9-2
	CRTC1	ENST00000594658.5	TSL:1	c.262G>A	p.Asp88Asn	missense	Exon 4 of 14	ENSP00000468893.1	M0QX46

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250228 AF XY: 0.00000739

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: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461076 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726856

African (AFR) AF: 0.00 AC: 0 AN: 33422

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111692

Other (OTH) AF: 0.0000166 AC: 1 AN: 60364

GnomAD4 genome Cov.: 31

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	Uncertain	0.37
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.75	D
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		9.2
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.16
Sift	Benign	0.10	T
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.24		Gain of MoRF binding (P = 0.0409)
MVP		0.68
MPC		0.60
ClinPred		0.86	D
GERP RS		4.8
Varity_R		0.18
gMVP		0.44
Mutation Taster		=64/36	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1177950459; hg19: chr19-18857866;