rs770215721

Variant names:

• chr19-18765446-G-A
• rs770215721
• NM_015321.3:c.929G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-18765446-G-A
• chr19-18765446-G-C
• chr19-18765446-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015321.3(CRTC1):​c.929G>A​(p.Gly310Asp) variant causes a missense 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G310A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRTC1 NM_015321.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05673641).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTC1	NM_015321.3	c.929G>A	p.Gly310Asp	missense_variant	Exon 9 of 14	ENST00000321949.13	NP_056136.2
CRTC1	NM_001098482.2	c.977G>A	p.Gly326Asp	missense_variant	Exon 10 of 15		NP_001091952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTC1	ENST00000321949.13	c.929G>A	p.Gly310Asp	missense_variant	Exon 9 of 14	1	NM_015321.3	ENSP00000323332.7
CRTC1	ENST00000338797.10	c.977G>A	p.Gly326Asp	missense_variant	Exon 10 of 15	1		ENSP00000345001.5
CRTC1	ENST00000594658.5	c.806G>A	p.Gly269Asp	missense_variant	Exon 9 of 14	1		ENSP00000468893.1
CRTC1	ENST00000601916.1	c.704G>A	p.Gly235Asp	missense_variant	Exon 8 of 10	5		ENSP00000469285.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Benign	0.83
DEOGEN2	Benign	0.28	T;.;.;.
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.85	T;D;D;D
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.057	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.8	L;.;.;.
PhyloP100		1.2
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.51	N;N;.;.
REVEL	Benign	0.042
Sift	Benign	0.13	T;T;.;.
Sift4G	Benign	0.28	T;T;T;T
Polyphen		0.0020	B;B;.;.
Vest4		0.30
MutPred		0.14		Gain of solvent accessibility (P = 0.039);.;.;.;
MVP		0.23
MPC		0.92
ClinPred		0.021	T
GERP RS		0.077
Varity_R		0.036
gMVP		0.25
Mutation Taster		=97/3	polymorphism

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: rs770215721; hg19: chr19-18876256;