chr16-75205488-A-G

Variant names:

• chr16-75205488-A-G
• NM_001025200.4:c.341T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001025200.4(CTRB2):​c.341T>C​(p.Ile114Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 5)
• Consequence: CTRB2 NM_001025200.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.321
• Publications: 0 publications found

Genes affected

CTRB2 (HGNC:2522): (chymotrypsinogen B2) This gene encodes a member of the serine protease family of enzymes and forms a principal precursor of the pancreatic proteolytic enzymes. The encoded preproprotein is synthesized in the acinar cells of the pancreas and secreted into the small intestine where it undergoes proteolytic activation to generate a functional enzyme. This CTRB2 gene is located head-to-head with the related CTRB1 gene. Some human populations have an alternate haplotype which inverts a 16.6 Kb region containing portions of intron 1, exon 1, and the upstream sequence of the CTRB1 and CTRB2 genes. In this inversion haplotype exon 1 and flanking sequence is swapped in CTRB1 and CTRB2. This inversion is associated with differential gene expression and increased risk for chronic pancreatitis. The GRCh38 assembly represents the minor allele for SNP rs8048956 of the CTRB1 gene. SNP rs8048956 is diagnostic for this inversion. [provided by RefSeq, Jan 2021]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.051562637).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025200.4. 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
	CTRB2	NM_001025200.4	MANE Select	c.341T>C	p.Ile114Thr	missense	Exon 5 of 7	NP_001020371.3	Q6GPI1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTRB2	ENST00000303037.13	TSL:1 MANE Select	c.341T>C	p.Ile114Thr	missense	Exon 5 of 7	ENSP00000303963.8	Q6GPI1
	CTRB2	ENST00000562106.5	TSL:3	c.80T>C	p.Ile27Thr	missense	Exon 2 of 4	ENSP00000454599.1	H3BMY1
	CTRB2	ENST00000562387.1	TSL:3	c.89T>C	p.Ile30Thr	missense	Exon 2 of 4	ENSP00000455207.1	H3BP92

Frequencies

GnomAD3 genomes Cov.: 5

GnomAD4 exome Cov.: 6

GnomAD4 genome Cov.: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	3.0
DANN	Benign	0.60
DEOGEN2	Benign	0.22	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.26	T
M_CAP	Uncertain	0.094	D
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	-0.070	N
PhyloP100		-0.32
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.26
Sift	Benign	0.44	T
Sift4G	Benign	0.64	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.43		Loss of stability (P = 0.0021)
MVP		0.36
MPC		0.12
ClinPred		0.063	T
GERP RS		-0.76
PromoterAI		-0.0084	Neutral
Varity_R		0.047
gMVP		0.27

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

hg19: chr16-75239386;