Variant 16-67931110-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001907.3(CTRL):c.144G>C(p.Gln48His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000373 in 1,614,074 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

CTRL
NM_001907.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.161

Variant links:

Genes affected

CTRL (HGNC:2524): (chymotrypsin like) This gene encodes a serine-type endopeptidase with chymotrypsin- and elastase-2-like activities. The gene encoding this zymogen is expressed specifically in the pancreas and likely functions as a digestive enzyme. [provided by RefSeq, Sep 2016]

CTRL links:

ENSG00000261884 (HGNC:):

ENSG00000261884 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016562313).

BP6

Variant 16-67931110-C-G is Benign according to our data. Variant chr16-67931110-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 785535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTRL	NM_001907.3 linkuse as main transcript	c.144G>C	p.Gln48His	missense_variant	2/7	ENST00000574481.6	NP_001898.1	P40313A0A024R6Z5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTRL	ENST00000574481.6 linkuse as main transcript	c.144G>C	p.Gln48His	missense_variant	2/7	1	NM_001907.3	ENSP00000458537.2		P40313
ENSG00000261884	ENST00000573493.1 linkuse as main transcript	n.*266-111G>C		intron_variant		3		ENSP00000463376.1		J3QL48

Frequencies

GnomAD3 genomes

AF:

0.00218

AC:

332

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000565

AC:

142

AN:

251234

Hom.:

AF XY:

0.000353

AC XY:

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.00856

Gnomad AMR exome

AF:

0.0000289

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:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000185

AC:

271

AN:

1461740

Hom.:

Cov.:

AF XY:

0.000138

AC XY:

100

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.00765

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.00217

AC:

331

AN:

152334

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

163

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00791

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000826

Hom.:

Bravo

AF:

0.00261

ESP6500AA

AF:

0.00933

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000708

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 18, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

T;D

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.91

D;D

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.017

T;T

MetaSVM

Benign

-0.55

MutationAssessor

Benign

0.45

N;.

PrimateAI

Benign

0.48

Sift4G

Pathogenic

0.0010

D;.

Polyphen

1.0

D;.

Vest4

0.65

MutPred

0.84

Gain of disorder (P = 0.1389);Gain of disorder (P = 0.1389);

MVP

0.94

MPC

0.51

ClinPred

0.13

GERP RS

0.13

Varity_R

0.68

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over