rs3098233

Variant names:

• chr8-103382516-T-C
• rs3098233
• NM_138455.4:c.648T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_138455.4(CTHRC1):​c.648T>C​(p.Gly216Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 1,612,944 control chromosomes in the GnomAD database, including 483,266 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.77 (45527 hom., cov: 32)
  • Exomes 𝑓: 0.77 (437739 hom.)
• Consequence: CTHRC1 NM_138455.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.905
• Publications: 27 publications found

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

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP7: Synonymous conserved (PhyloP=-0.905 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTHRC1	NM_138455.4	MANE Select	c.648T>C	p.Gly216Gly	synonymous	Exon 4 of 4	NP_612464.1
	CTHRC1	NM_001256099.2		c.606T>C	p.Gly202Gly	synonymous	Exon 4 of 4	NP_001243028.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTHRC1	ENST00000330295.10	TSL:1 MANE Select	c.648T>C	p.Gly216Gly	synonymous	Exon 4 of 4	ENSP00000330523.5
	CTHRC1	ENST00000520337.1	TSL:1	c.606T>C	p.Gly202Gly	synonymous	Exon 4 of 4	ENSP00000430550.1
	CTHRC1	ENST00000520880.1	TSL:4	c.258T>C	p.Gly86Gly	synonymous	Exon 3 of 3	ENSP00000430399.1

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117458 AN: 152014 Hom.: 45492 Cov.: 32

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.834

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.769

GnomAD2 exomes AF: 0.763 AC: 191915 AN: 251438 AF XY: 0.763

Gnomad AFR exome AF: 0.783

Gnomad AMR exome AF: 0.765

Gnomad ASJ exome AF: 0.818

Gnomad EAS exome AF: 0.671

Gnomad FIN exome AF: 0.734

Gnomad NFE exome AF: 0.778

Gnomad OTH exome AF: 0.767

GnomAD4 exome AF: 0.773 AC: 1129758 AN: 1460812 Hom.: 437739 Cov.: 40 AF XY: 0.773 AC XY: 561626 AN XY: 726784

African (AFR) AF: 0.792 AC: 26487 AN: 33446

American (AMR) AF: 0.764 AC: 34159 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 21560 AN: 26108

East Asian (EAS) AF: 0.640 AC: 25326 AN: 39596

South Asian (SAS) AF: 0.754 AC: 65031 AN: 86242

European-Finnish (FIN) AF: 0.739 AC: 39452 AN: 53408

Middle Eastern (MID) AF: 0.837 AC: 4823 AN: 5762

European-Non Finnish (NFE) AF: 0.779 AC: 865820 AN: 1111176

Other (OTH) AF: 0.780 AC: 47100 AN: 60356

GnomAD4 genome AF: 0.773 AC: 117541 AN: 152132 Hom.: 45527 Cov.: 32 AF XY: 0.768 AC XY: 57135 AN XY: 74378

African (AFR) AF: 0.784 AC: 32533 AN: 41486

American (AMR) AF: 0.764 AC: 11692 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.825 AC: 2860 AN: 3468

East Asian (EAS) AF: 0.656 AC: 3391 AN: 5168

South Asian (SAS) AF: 0.759 AC: 3659 AN: 4822

European-Finnish (FIN) AF: 0.724 AC: 7656 AN: 10580

Middle Eastern (MID) AF: 0.825 AC: 241 AN: 292

European-Non Finnish (NFE) AF: 0.782 AC: 53159 AN: 68002

Other (OTH) AF: 0.770 AC: 1625 AN: 2110

Alfa AF: 0.780 Hom.: 91222

Bravo AF: 0.776

Asia WGS AF: 0.694 AC: 2416 AN: 3478

EpiCase AF: 0.780

EpiControl AF: 0.778

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.2
DANN	Benign	0.56
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3098233; hg19: chr8-104394744; COSMIC: COSV57715560; COSMIC: COSV57715560;