8-103376218-A-G

Variant names:

• chr8-103376218-A-G
• rs35500845
• NM_138455.4:c.372+259A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138455.4(CTHRC1):​c.372+259A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0677 in 152,268 control chromosomes in the GnomAD database, including 446 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 0.068 (446 hom., cov: 33)
• Consequence: CTHRC1 NM_138455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.379
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTHRC1	NM_138455.4	c.372+259A>G		intron_variant	Intron 2 of 3	ENST00000330295.10	NP_612464.1
CTHRC1	NM_001256099.2	c.330+259A>G		intron_variant	Intron 2 of 3		NP_001243028.1
CTHRC1	XM_011516824.3	c.372+259A>G		intron_variant	Intron 2 of 2		XP_011515126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTHRC1	ENST00000330295.10	c.372+259A>G		intron_variant	Intron 2 of 3	1	NM_138455.4	ENSP00000330523.5
CTHRC1	ENST00000520337.1	c.330+259A>G		intron_variant	Intron 2 of 3	1		ENSP00000430550.1
CTHRC1	ENST00000415886.2	c.*187A>G		downstream_gene_variant		2		ENSP00000416045.2

Frequencies

GnomAD3 genomes AF: 0.0677 AC: 10299 AN: 152150 Hom.: 446 Cov.: 33

Gnomad AFR AF: 0.0182

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.0571

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.00904

Gnomad SAS AF: 0.0754

Gnomad FIN AF: 0.0923

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0963

Gnomad OTH AF: 0.0761

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0677 AC: 10311 AN: 152268 Hom.: 446 Cov.: 33 AF XY: 0.0679 AC XY: 5052 AN XY: 74442

African (AFR) AF: 0.0184 AC: 765 AN: 41560

American (AMR) AF: 0.0571 AC: 873 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 410 AN: 3470

East Asian (EAS) AF: 0.00906 AC: 47 AN: 5188

South Asian (SAS) AF: 0.0765 AC: 369 AN: 4822

European-Finnish (FIN) AF: 0.0923 AC: 978 AN: 10598

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0963 AC: 6547 AN: 68016

Other (OTH) AF: 0.0763 AC: 161 AN: 2110

Alfa AF: 0.0420 Hom.: 31

Bravo AF: 0.0637

Asia WGS AF: 0.0350 AC: 120 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.1
DANN	Benign	0.87
PhyloP100		0.38
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: rs35500845; hg19: chr8-104388446;