Variant chr16-67930946-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001907.3(CTRL):c.210G>T(p.Val70Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,613,808 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 19 hom., cov: 32)

Exomes 𝑓: 0.00078 ( 14 hom. )

Consequence

CTRL
NM_001907.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.68

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008068621).

BP6

Variant 16-67930946-C-A is Benign according to our data. Variant chr16-67930946-C-A is described in ClinVar as [Benign]. Clinvar id is 709489.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.68 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00715 (1089/152282) while in subpopulation AFR AF= 0.0249 (1036/41552). AF 95% confidence interval is 0.0237. There are 19 homozygotes in gnomad4. There are 511 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTRL	NM_001907.3 linkuse as main transcript	c.210G>T	p.Val70Val	synonymous_variant	3/7	ENST00000574481.6	NP_001898.1	P40313A0A024R6Z5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CTRL	ENST00000574481.6 linkuse as main transcript	c.210G>T	p.Val70Val	synonymous_variant	3/7	1	NM_001907.3	ENSP00000458537.2	P40313
ENSG00000261884	ENST00000573493.1 linkuse as main transcript	n.*319G>T		non_coding_transcript_exon_variant	5/5	3		ENSP00000463376.1	J3QL48
ENSG00000261884	ENST00000573493.1 linkuse as main transcript	n.*319G>T		3_prime_UTR_variant	5/5	3		ENSP00000463376.1	J3QL48

Frequencies

GnomAD3 genomes

AF:

0.00716

AC:

1089

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0250

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

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:

0.000162

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00187

AC:

470

AN:

250942

Hom.:

AF XY:

0.00130

AC XY:

176

AN XY:

135616

show subpopulations

Gnomad AFR exome

AF:

0.0251

Gnomad AMR exome

AF:

0.00133

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:

0.000114

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000781

AC:

1141

AN:

1461526

Hom.:

Cov.:

AF XY:

0.000704

AC XY:

512

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.0261

Gnomad4 AMR exome

AF:

0.00134

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:

0.0000944

Gnomad4 OTH exome

AF:

0.00159

GnomAD4 genome

AF:

0.00715

AC:

1089

AN:

152282

Hom.:

Cov.:

AF XY:

0.00686

AC XY:

511

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0249

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00253

Hom.:

Bravo

AF:

0.00791

ESP6500AA

AF:

0.0284

AC:

125

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00241

AC:

293

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 31, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

6.1

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.27

MetaRNN

Benign

0.0081

Sift4G

Uncertain

0.056

MVP

0.97

GERP RS

1.9

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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