rs41307798

Positions:

• chr1-15442501-C-G
• chr1-15442501-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007272.3(CTRC):​c.285C>G​(p.Asp95Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D95D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CTRC NM_007272.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.81

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048345417).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTRC	NM_007272.3	c.285C>G	p.Asp95Glu	missense_variant	4/8	ENST00000375949.5	NP_009203.2
CTRC	XM_011540550.2	c.285C>G	p.Asp95Glu	missense_variant	4/7		XP_011538852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTRC	ENST00000375949.5	c.285C>G	p.Asp95Glu	missense_variant	4/8	1	NM_007272.3	ENSP00000365116	P1
CTRC	ENST00000375943.6	c.95C>G	p.Thr32Arg	missense_variant	2/5	1		ENSP00000365110
CTRC	ENST00000476813.5	n.107C>G		non_coding_transcript_exon_variant	2/3	3
CTRC	ENST00000483406.1	n.195C>G		non_coding_transcript_exon_variant	3/6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251370 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135858

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461846 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	0.0030
DANN	Benign	0.46
DEOGEN2	Benign	0.13	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.21	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.25
Sift	Benign	1.0	T
Sift4G	Benign	0.75	T
Polyphen		0.0	B
Vest4		0.19
MutPred		0.35		Gain of disorder (P = 0.1132);
MVP		0.58
MPC		0.17
ClinPred		0.026	T
GERP RS		-6.2
Varity_R		0.14
gMVP		0.49

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: rs41307798; hg19: chr1-15768997;