NM_138455.4:c.250G>C

Variant names:

• chr8-103375837-G-C
• rs1287051433
• NM_138455.4:c.250G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_138455.4(CTHRC1):​c.250G>C​(p.Asp84His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CTHRC1 NM_138455.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.60

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.838

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTHRC1	NM_138455.4	c.250G>C	p.Asp84His	missense_variant	Exon 2 of 4	ENST00000330295.10	NP_612464.1
CTHRC1	NM_001256099.2	c.208G>C	p.Asp70His	missense_variant	Exon 2 of 4		NP_001243028.1
CTHRC1	XM_011516824.3	c.250G>C	p.Asp84His	missense_variant	Exon 2 of 3		XP_011515126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTHRC1	ENST00000330295.10	c.250G>C	p.Asp84His	missense_variant	Exon 2 of 4	1	NM_138455.4	ENSP00000330523.5
CTHRC1	ENST00000520337.1	c.208G>C	p.Asp70His	missense_variant	Exon 2 of 4	1		ENSP00000430550.1
CTHRC1	ENST00000415886.2	c.250G>C	p.Asp84His	missense_variant	Exon 2 of 2	2		ENSP00000416045.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251488 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135916

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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461864 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D;D;.
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D;T
M_CAP	Pathogenic	0.36	D
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Uncertain	2.7	M;.;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.2	D;D;D
REVEL	Pathogenic	0.80
Sift	Benign	0.066	T;D;T
Sift4G	Uncertain	0.0090	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.80
MutPred		0.50		Loss of loop (P = 0.1258);Loss of loop (P = 0.1258);.;
MVP		0.97
MPC		0.81
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.45
gMVP		0.64

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: rs1287051433; hg19: chr8-104388065;