chr8-103371660-C-A

Variant names:

• chr8-103371660-C-A
• rs202192964
• NM_138455.4:c.4C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_138455.4(CTHRC1):​c.4C>A​(p.Arg2Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000029 in 1,381,646 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: CTHRC1 NM_138455.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 1 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]

BAALC-AS1 (HGNC:50461): (BAALC antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP7: Synonymous conserved (PhyloP=1.51 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTHRC1	NM_138455.4	MANE Select	c.4C>A	p.Arg2Arg	synonymous	Exon 1 of 4	NP_612464.1	Q96CG8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTHRC1	ENST00000330295.10	TSL:1 MANE Select	c.4C>A	p.Arg2Arg	synonymous	Exon 1 of 4	ENSP00000330523.5	Q96CG8-1
	CTHRC1	ENST00000891015.1		c.4C>A	p.Arg2Arg	synonymous	Exon 1 of 4	ENSP00000561074.1
	CTHRC1	ENST00000415886.2	TSL:2	c.4C>A	p.Arg2Arg	synonymous	Exon 1 of 2	ENSP00000416045.2	E7EVQ5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000290 AC: 4 AN: 1381646 Hom.: 0 Cov.: 31 AF XY: 0.00000147 AC XY: 1 AN XY: 681264

African (AFR) AF: 0.00 AC: 0 AN: 28918

American (AMR) AF: 0.00 AC: 0 AN: 34698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24478

East Asian (EAS) AF: 0.00 AC: 0 AN: 33934

South Asian (SAS) AF: 0.00 AC: 0 AN: 77578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4020

European-Non Finnish (NFE) AF: 0.00000279 AC: 3 AN: 1073638

Other (OTH) AF: 0.0000175 AC: 1 AN: 57148

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	11
DANN	Benign	0.91
PhyloP100		1.5
PromoterAI		0.046	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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: rs202192964; hg19: chr8-104383888;