rs3098233

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 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. Variant has been reported in Lovd as Benign (no stars).

• 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

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 8-103382516-T-C is Benign according to our data. Variant chr8-103382516-T-C is described in Lovd as [Benign].
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTHRC1	NM_138455.4	c.648T>C	p.Gly216Gly	synonymous_variant	Exon 4 of 4	ENST00000330295.10	NP_612464.1
CTHRC1	NM_001256099.2	c.606T>C	p.Gly202Gly	synonymous_variant	Exon 4 of 4		NP_001243028.1
CTHRC1	XM_011516824.3	c.*23T>C		3_prime_UTR_variant	Exon 3 of 3		XP_011515126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTHRC1	ENST00000330295.10	c.648T>C	p.Gly216Gly	synonymous_variant	Exon 4 of 4	1	NM_138455.4	ENSP00000330523.5
CTHRC1	ENST00000520337.1	c.606T>C	p.Gly202Gly	synonymous_variant	Exon 4 of 4	1		ENSP00000430550.1
CTHRC1	ENST00000520880.1	c.258T>C	p.Gly86Gly	synonymous_variant	Exon 3 of 3	4		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

GnomAD3 exomes AF: 0.763 AC: 191915 AN: 251438 Hom.: 73502 AF XY: 0.763 AC XY: 103709 AN XY: 135886

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 SAS exome AF: 0.752

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

Gnomad4 AFR exome AF: 0.792

Gnomad4 AMR exome AF: 0.764

Gnomad4 ASJ exome AF: 0.826

Gnomad4 EAS exome AF: 0.640

Gnomad4 SAS exome AF: 0.754

Gnomad4 FIN exome AF: 0.739

Gnomad4 NFE exome AF: 0.779

Gnomad4 OTH exome AF: 0.780

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

Gnomad4 AFR AF: 0.784

Gnomad4 AMR AF: 0.764

Gnomad4 ASJ AF: 0.825

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.759

Gnomad4 FIN AF: 0.724

Gnomad4 NFE AF: 0.782

Gnomad4 OTH AF: 0.770

Alfa AF: 0.781 Hom.: 75303

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.2
DANN	Benign	0.56

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

LitVar

Other links and lift over

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