1-15440369-G-C

Variant names:

• chr1-15440369-G-C
• rs145868278
• NM_007272.3:c.110G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007272.3(CTRC):​c.110G>C​(p.Arg37Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,940 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R37W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CTRC NM_007272.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.893
• Publications: 8 publications found

Genes affected

CTRC (HGNC:2523): (chymotrypsin C) This gene encodes a member of the peptidase S1 family. The encoded protein is a serum calcium-decreasing factor that has chymotrypsin-like protease activity. Alternatively spliced transcript variants have been observed, but their full-length nature has not been determined. [provided by RefSeq, Jul 2008]

CTRC Gene-Disease associations (from GenCC):

• hereditary chronic pancreatitis

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22348604).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007272.3. 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
	CTRC	NM_007272.3	MANE Select	c.110G>C	p.Arg37Pro	missense	Exon 2 of 8	NP_009203.2	Q99895

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTRC	ENST00000375949.5	TSL:1 MANE Select	c.110G>C	p.Arg37Pro	missense	Exon 2 of 8	ENSP00000365116.4	Q99895
	CTRC	ENST00000375943.6	TSL:1	c.40+1865G>C		intron	N/A	ENSP00000365110.2	Q68DR9
	CTRC	ENST00000483406.1	TSL:5	n.20G>C		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459940 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726146

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44486

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26030

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 85878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53156

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5498

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111510

Other (OTH) AF: 0.00 AC: 0 AN: 60262

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	6.6
DANN	Benign	0.64
DEOGEN2	Uncertain	0.43	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.65	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	-0.53	N
PhyloP100		-0.89
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.34
Sift	Benign	0.20	T
Sift4G	Benign	0.29	T
Polyphen		0.083	B
Vest4		0.38
MutPred		0.49		Gain of glycosylation at P38 (P = 0.0552)
MVP		0.45
MPC		0.55
ClinPred		0.28	T
GERP RS		-4.1
Varity_R		0.54
gMVP		0.73
Mutation Taster		=92/8	polymorphism

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: rs145868278; hg19: chr1-15766865;