rs760937

Variant names:

• chr1-15446675-A-C
• rs760937
• NM_007272.3:c.*86A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-15446675-A-C
• chr1-15446675-A-G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS2_Supporting

The NM_007272.3(CTRC):​c.*86A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000748 in 1,336,188 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: 0.0000075 (0 hom.)
• Consequence: CTRC NM_007272.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98
• Publications: 3 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BS2: High AC in GnomAdExome4 at 10 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTRC	NM_007272.3	c.*86A>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000375949.5	NP_009203.2
CTRC	XM_011540550.2	c.747A>C	p.Ala249Ala	synonymous_variant	Exon 7 of 7		XP_011538852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTRC	ENST00000375949.5	c.*86A>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_007272.3	ENSP00000365116.4
CTRC	ENST00000375943.6	c.*347A>C		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000365110.2
CTRC	ENST00000483406.1	n.*21A>C		downstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250166 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000748 AC: 10 AN: 1336188 Hom.: 0 Cov.: 20 AF XY: 0.0000104 AC XY: 7 AN XY: 671356

African (AFR) AF: 0.00 AC: 0 AN: 30860

American (AMR) AF: 0.0000449 AC: 2 AN: 44536

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25378

East Asian (EAS) AF: 0.00 AC: 0 AN: 39166

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83632

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53180

Middle Eastern (MID) AF: 0.000723 AC: 4 AN: 5530

European-Non Finnish (NFE) AF: 0.00000301 AC: 3 AN: 997576

Other (OTH) AF: 0.00 AC: 0 AN: 56330

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.40
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs760937; hg19: chr1-15773170;