Variant 8-103378079-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_138455.4(CTHRC1):c.425G>A(p.Ser142Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

CTHRC1
NM_138455.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.68

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_benign. Variant got -1 ACMG points.

BS2

High AC in GnomAdExome4 at 9 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 link	c.425G>A	p.Ser142Asn	missense_variant	3/4	ENST00000330295.10	NP_612464.1	Q96CG8-1
CTHRC1	NM_001256099.2 link	c.383G>A	p.Ser128Asn	missense_variant	3/4		NP_001243028.1	Q96CG8-3
CTHRC1	XM_011516824.3 link	c.372+2120G>A		intron_variant			XP_011515126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CTHRC1	ENST00000330295.10 link	c.425G>A	p.Ser142Asn	missense_variant	3/4	1	NM_138455.4	ENSP00000330523.5	Q96CG8-1
CTHRC1	ENST00000520337.1 link	c.383G>A	p.Ser128Asn	missense_variant	3/4	1		ENSP00000430550.1	Q96CG8-3
CTHRC1	ENST00000520880.1 link	c.35G>A	p.Ser12Asn	missense_variant	2/3	4		ENSP00000430399.1	E5RK99

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 14, 2023

The c.425G>A (p.S142N) alteration is located in exon 3 (coding exon 3) of the CTHRC1 gene. This alteration results from a G to A substitution at nucleotide position 425, causing the serine (S) at amino acid position 142 to be replaced by an asparagine (N). 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

Uncertain

0.49

BayesDel_addAF

Benign

-0.042

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.12

T;.;.

Eigen

Benign

0.047

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.57

D;D;D

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.1

L;.;.

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

0.20

N;N;N

REVEL

Benign

0.10

Sift

Benign

0.58

T;T;T

Sift4G

Benign

0.38

T;T;T

Polyphen

0.30

B;.;.

Vest4

0.74

MutPred

0.27

Loss of catalytic residue at S142 (P = 0.0336);.;.;

MVP

0.69

MPC

0.18

ClinPred

0.66

GERP RS

5.5

Varity_R

0.21

gMVP

0.72

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over