1-10450270-C-G

Variant names:

• chr1-10450270-C-G
• rs774882640
• NM_001302.5:c.47C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001302.5(CORT):​c.47C>G​(p.Thr16Arg) 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. 14/20 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. T16M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CORT NM_001302.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326
• Publications: 1 publications found

Genes affected

CORT (HGNC:2257): (cortistatin) This gene encodes a neuropeptide that is structurally similar to somatostatin. It binds to all known somatostatin receptors, and shares many pharmacological and functional properties with somatostatin, including the depression of neuronal activity. However, it also has many properties distinct from somatostatin, such as induction of slow-wave sleep, apparently by antagonism of the excitatory effects of acetylcholine on the cortex, reduction of locomotor activity, and activation of cation selective currents not responsive to somatostatin. The preproprotein undergoes further processing into multiple mature products. Read-through transcripts exist between this gene and the upstream APITD1 (apoptosis-inducing, TAF9-like domain 1) gene, as represented in GeneID:100526739. [provided by RefSeq, Nov 2010]

CENPS-CORT (HGNC:38843): (CENPS-CORT readthrough) This locus represents naturally occurring read-through transcription between the neighboring APITD1 (apoptosis-inducing, TAF9-like domain 1) and CORT (cortistatin) genes. Alternative splicing results in multiple transcript variants, two of which encode fusion proteins that share sequence identity with the products of each individual gene. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13092887).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001302.5. 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
	CORT	NM_001302.5	MANE Select	c.47C>G	p.Thr16Arg	missense	Exon 1 of 2	NP_001293.3
	CENPS-CORT	NM_198544.4		c.277-1107C>G		intron	N/A	NP_940946.1
	CENPS-CORT	NM_001243768.2		c.214-1107C>G		intron	N/A	NP_001230697.1	A0A087WT10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORT	ENST00000377049.4	TSL:1 MANE Select	c.47C>G	p.Thr16Arg	missense	Exon 1 of 2	ENSP00000366248.4	O00230
	CENPS-CORT	ENST00000602787.6	TSL:3	c.*37-1107C>G		intron	N/A	ENSP00000473509.2
	CENPS-CORT	ENST00000400900.6	TSL:2	c.277-1107C>G		intron	N/A	ENSP00000383692.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	7.6
DANN	Uncertain	0.98
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.33
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.10
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.65	T
Polyphen		0.94	P
Vest4		0.26
MutPred		0.21		Loss of helix (P = 0.0093)
MVP		0.072
MPC		0.030
ClinPred		0.31	T
GERP RS		-1.8
PromoterAI		-0.044	Neutral
Varity_R		0.12
gMVP		0.096
Mutation Taster		=95/5	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: rs774882640; hg19: chr1-10510327;