8-103375958-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_138455.4(CTHRC1):c.371C>T(p.Ala124Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000323 in 1,608,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

CTHRC1
NM_138455.4 missense, splice_region

Scores

Splicing: ADA: 0.001708

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.77

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

Barrett esophagus
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CTHRC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.63347 (below the threshold of 3.09). Trascript score misZ: 0.39942 (below the threshold of 3.09). GenCC associations: The gene is linked to Barrett esophagus.

BP4

Computational evidence support a benign effect (MetaRNN=0.079436034).

BS2

High AC in GnomAdExome4 at 48 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138455.4. 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
	CTHRC1	NM_138455.4	MANE Select	c.371C>T	p.Ala124Val	missense splice_region	Exon 2 of 4	NP_612464.1	Q96CG8-1
	CTHRC1	NM_001256099.2		c.329C>T	p.Ala110Val	missense splice_region	Exon 2 of 4	NP_001243028.1	Q96CG8-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTHRC1	ENST00000330295.10	TSL:1 MANE Select	c.371C>T	p.Ala124Val	missense splice_region	Exon 2 of 4	ENSP00000330523.5	Q96CG8-1
CTHRC1	ENST00000520337.1	TSL:1	c.329C>T	p.Ala110Val	missense splice_region	Exon 2 of 4	ENSP00000430550.1	Q96CG8-3
CTHRC1	ENST00000415886.2	TSL:2	c.371C>T	p.Ala124Val	missense	Exon 2 of 2	ENSP00000416045.2	E7EVQ5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151872

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000968

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

GnomAD2 exomes

AF:

0.0000848

AC:

AN:

247724

AF XY:

0.0000897

show subpopulations

Gnomad AFR exome

AF:

0.0000626

Gnomad AMR exome

AF:

0.000381

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000466

Gnomad NFE exome

AF:

0.0000358

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000330

AC:

AN:

1456264

Hom.:

Cov.:

AF XY:

0.0000373

AC XY:

AN XY:

724456

show subpopulations

African (AFR)

AF:

0.0000899

AC:

AN:

33372

American (AMR)

AF:

0.000382

AC:

AN:

44464

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26034

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.0000349

AC:

AN:

85950

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53300

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000199

AC:

AN:

1107500

Other (OTH)

AF:

0.0000332

AC:

AN:

60212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

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:

0.0000263

AC:

AN:

151990

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41434

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10540

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67988

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.0000329

Hom.:

Bravo

AF:

0.0000491

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000989

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.31

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.12

Eigen

Benign

-0.081

Eigen_PC

Benign

0.031

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.81

M_CAP

Benign

0.036

MetaRNN

Benign

0.079

MetaSVM

Benign

-0.64

MutationAssessor

Benign

0.66

PhyloP100

4.8

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.10

REVEL

Benign

0.13

Sift

Benign

0.69

Sift4G

Benign

0.70

Polyphen

0.81

Vest4

0.36

MVP

0.80

MPC

0.21

ClinPred

0.18

GERP RS

4.8

Varity_R

0.036

gMVP

0.59

Mutation Taster

=78/22

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0017

dbscSNV1_RF

Benign

0.17

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

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