chr19-18765436-C-T

Variant names:

• chr19-18765436-C-T
• rs1274858564
• NM_015321.3:c.919C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_015321.3(CRTC1):​c.919C>T​(p.Arg307Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,752 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: CRTC1 NM_015321.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.89
• Publications: 1 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 -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 7 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.919C>T	p.Arg307Cys	missense	Exon 9 of 14	NP_056136.2	Q6UUV9-1
	CRTC1	NM_001098482.2		c.967C>T	p.Arg323Cys	missense	Exon 10 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.919C>T	p.Arg307Cys	missense	Exon 9 of 14	ENSP00000323332.7	Q6UUV9-1
	CRTC1	ENST00000338797.10	TSL:1	c.967C>T	p.Arg323Cys	missense	Exon 10 of 15	ENSP00000345001.5	Q6UUV9-2
	CRTC1	ENST00000594658.5	TSL:1	c.796C>T	p.Arg266Cys	missense	Exon 9 of 14	ENSP00000468893.1	M0QX46

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000200 AC: 5 AN: 250544 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000582

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1460752 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 726710

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.0000448 AC: 2 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52704

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111772

Other (OTH) AF: 0.0000166 AC: 1 AN: 60370

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000571 Hom.: 0

Bravo AF: 0.0000113

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	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.83	D
Eigen	Benign	0.12
Eigen_PC	Benign	0.043
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.9
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.13
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.040	D
Polyphen		0.98	D
Vest4		0.68
MutPred		0.19		Loss of glycosylation at S303 (P = 0.1092)
MVP		0.38
MPC		1.7
ClinPred		0.87	D
GERP RS		3.1
Varity_R		0.34
gMVP		0.61
Mutation Taster		=69/31	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: rs1274858564; hg19: chr19-18876246;