dbSNP rs764595813: CTHRC1:p.Arg156Gly (chr8-103378120-C-G) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_138455.4(CTHRC1):c.466C>G(p.Arg156Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R156H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CTHRC1
NM_138455.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.68

Variant links:

Genes affected

CTHRC1 (HGNC:18831): (collagen triple helix repeat containing 1) This locus encodes a protein that may play a role in the cellular response to arterial injury through involvement in vascular remodeling. Mutations at this locus have been associated with Barrett esophagus and esophageal adenocarcinoma. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2012]

CTHRC1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.962

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTHRC1	NM_138455.4 link	c.466C>G	p.Arg156Gly	missense_variant	Exon 3 of 4	ENST00000330295.10	NP_612464.1	Q96CG8-1
CTHRC1	NM_001256099.2 link	c.424C>G	p.Arg142Gly	missense_variant	Exon 3 of 4		NP_001243028.1	Q96CG8-3
CTHRC1	XM_011516824.3 link	c.372+2161C>G		intron_variant	Intron 2 of 2		XP_011515126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CTHRC1	ENST00000330295.10 link	c.466C>G	p.Arg156Gly	missense_variant	Exon 3 of 4	1	NM_138455.4	ENSP00000330523.5	Q96CG8-1
CTHRC1	ENST00000520337.1 link	c.424C>G	p.Arg142Gly	missense_variant	Exon 3 of 4	1		ENSP00000430550.1	Q96CG8-3
CTHRC1	ENST00000520880.1 link	c.76C>G	p.Arg26Gly	missense_variant	Exon 2 of 3	4		ENSP00000430399.1	E5RK99

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461774

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.39

BayesDel_noAF

Pathogenic

0.32

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.74

D;.;.

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Uncertain

0.23

MetaRNN

Pathogenic

0.96

D;D;D

MetaSVM

Uncertain

0.36

MutationAssessor

Uncertain

2.8

M;.;.

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-6.5

D;D;D

REVEL

Pathogenic

0.81

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.93

MutPred

0.86

Loss of MoRF binding (P = 0.0449);.;.;

MVP

0.91

MPC

0.86

ClinPred

1.0

GERP RS

5.3

Varity_R

0.91

gMVP

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over