Variant 8-103371790-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting

The NM_138455.4(CTHRC1):c.134G>A(p.Arg45Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000101 in 1,379,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

CTHRC1
NM_138455.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.59

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11615759).

BS2

High AC in GnomAdExome4 at 14 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTHRC1	NM_138455.4 linkuse as main transcript	c.134G>A	p.Arg45Lys	missense_variant	1/4	ENST00000330295.10	NP_612464.1	Q96CG8-1
CTHRC1	XM_011516824.3 linkuse as main transcript	c.134G>A	p.Arg45Lys	missense_variant	1/3		XP_011515126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTHRC1	ENST00000330295.10 linkuse as main transcript	c.134G>A	p.Arg45Lys	missense_variant	1/4	1	NM_138455.4	ENSP00000330523.5		Q96CG8-1
CTHRC1	ENST00000415886.2 linkuse as main transcript	c.134G>A	p.Arg45Lys	missense_variant	1/2	2		ENSP00000416045.2		E7EVQ5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000155

AC:

AN:

128642

Hom.:

AF XY:

0.0000144

AC XY:

AN XY:

69274

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000442

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000101

AC:

AN:

1379702

Hom.:

Cov.:

AF XY:

0.00000589

AC XY:

AN XY:

679642

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000293

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000112

Gnomad4 OTH exome

AF:

0.0000175

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 12, 2021

The c.134G>A (p.R45K) alteration is located in exon 1 (coding exon 1) of the CTHRC1 gene. This alteration results from a G to A substitution at nucleotide position 134, causing the arginine (R) at amino acid position 45 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

0.0030

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.027

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.61

T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.81

L;.

MutationTaster

Benign

0.64

D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.35

N;N

REVEL

Benign

0.13

Sift

Benign

0.42

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.0

B;B

Vest4

0.28

MutPred

0.23

Gain of methylation at R45 (P = 0.0255);Gain of methylation at R45 (P = 0.0255);

MVP

0.81

MPC

0.19

ClinPred

0.31

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.20

gMVP

0.39

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over