1-10450312-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001302.5(CORT):c.89G>A(p.Arg30Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,514,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000081 ( 0 hom. )

Consequence

CORT
NM_001302.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0650

Publications

0 publications found

Variant links:

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]

CORT links:

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]

CENPS-CORT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.023737133).

BP6

Variant 1-10450312-G-A is Benign according to our data. Variant chr1-10450312-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2482329.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CORT	NM_001302.5	MANE Select	c.89G>A	p.Arg30Gln	missense	Exon 1 of 2	NP_001293.3
CENPS-CORT	NM_198544.4		c.277-1065G>A		intron	N/A	NP_940946.1
CENPS-CORT	NM_001243768.2		c.214-1065G>A		intron	N/A	NP_001230697.1	A0A087WT10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CORT	ENST00000377049.4	TSL:1 MANE Select	c.89G>A	p.Arg30Gln	missense	Exon 1 of 2	ENSP00000366248.4	O00230
CENPS-CORT	ENST00000602787.6	TSL:3	c.*37-1065G>A		intron	N/A	ENSP00000473509.2
CENPS-CORT	ENST00000400900.6	TSL:2	c.277-1065G>A		intron	N/A	ENSP00000383692.2

Frequencies

GnomAD3 genomes

AF:

0.0000525

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000176

AC:

AN:

170514

AF XY:

0.00

show subpopulations

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:

0.0000359

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000808

AC:

AN:

1361868

Hom.:

Cov.:

AF XY:

0.00000898

AC XY:

AN XY:

668242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30102

American (AMR)

AF:

0.00

AC:

AN:

29252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20282

East Asian (EAS)

AF:

0.0000264

AC:

AN:

37898

South Asian (SAS)

AF:

0.00

AC:

AN:

69122

European-Finnish (FIN)

AF:

0.0000202

AC:

AN:

49562

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5294

European-Non Finnish (NFE)

AF:

0.00000846

AC:

AN:

1064172

Other (OTH)

AF:

0.00

AC:

AN:

56184

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0000723

AC:

AN:

41472

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000167

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.14

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.18

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0068

LIST_S2

Benign

0.40

M_CAP

Benign

0.0028

MetaRNN

Benign

0.024

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.4

PhyloP100

-0.065

PROVEAN

Benign

1.3

REVEL

Benign

0.014

Sift

Benign

0.70

Sift4G

Benign

0.38

Polyphen

0.0010

Vest4

0.062

MVP

0.20

MPC

0.030

ClinPred

0.034

GERP RS

-2.9

PromoterAI

0.0098

Neutral

(source)

Varity_R

0.024

gMVP

0.048

Mutation Taster

=99/1

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over