NM_138455.4:c.467G>A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP3BP4_ModerateBS2
The NM_138455.4(CTHRC1):c.467G>A(p.Arg156His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000188 in 1,614,162 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Consequence
NM_138455.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CTHRC1 | NM_138455.4 | c.467G>A | p.Arg156His | missense_variant | Exon 3 of 4 | ENST00000330295.10 | NP_612464.1 | |
CTHRC1 | NM_001256099.2 | c.425G>A | p.Arg142His | missense_variant | Exon 3 of 4 | NP_001243028.1 | ||
CTHRC1 | XM_011516824.3 | c.372+2162G>A | 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.467G>A | p.Arg156His | missense_variant | Exon 3 of 4 | 1 | NM_138455.4 | ENSP00000330523.5 | ||
CTHRC1 | ENST00000520337.1 | c.425G>A | p.Arg142His | missense_variant | Exon 3 of 4 | 1 | ENSP00000430550.1 | |||
CTHRC1 | ENST00000520880.1 | c.77G>A | p.Arg26His | missense_variant | Exon 2 of 3 | 4 | ENSP00000430399.1 |
Frequencies
GnomAD3 genomes AF: 0.000841 AC: 128AN: 152212Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000334 AC: 84AN: 251242Hom.: 0 AF XY: 0.000214 AC XY: 29AN XY: 135822
GnomAD4 exome AF: 0.000121 AC: 177AN: 1461832Hom.: 1 Cov.: 32 AF XY: 0.000118 AC XY: 86AN XY: 727222
GnomAD4 genome AF: 0.000834 AC: 127AN: 152330Hom.: 0 Cov.: 32 AF XY: 0.000644 AC XY: 48AN XY: 74486
ClinVar
Submissions by phenotype
not provided Uncertain:1
The CTHRC1 p.Arg142His variant was not identified in the literature nor was it identified in ClinVar, Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs145062750) and was found in control databases in 113 of 282640 chromosomes at a frequency of 0.0004 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 87 of 24968 chromosomes (freq: 0.003484), South Asian in 18 of 30612 chromosomes (freq: 0.000588), Other in 1 of 7218 chromosomes (freq: 0.000139), Latino in 2 of 35436 chromosomes (freq: 0.000056), East Asian in 1 of 19952 chromosomes (freq: 0.00005) and European (non-Finnish) in 4 of 128968 chromosomes (freq: 0.000031), while the variant was not observed in the Ashkenazi Jewish and European (Finnish) populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. The p.Arg142 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at