20-18542358-C-G

Position:

chr20-18542358-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006363.6(SEC23B):c.1467C>G(p.His489Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,614,028 control chromosomes in the GnomAD database, including 11,624 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1301 hom., cov: 33)

Exomes 𝑓: 0.11 ( 10323 hom. )

Consequence

SEC23B
NM_006363.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.0430

Variant links:

Genes affected

SEC23B (HGNC:10702): (SEC23 homolog B, COPII coat complex component) The protein encoded by this gene is a member of the SEC23 subfamily of the SEC23/SEC24 family, which is involved in vesicle trafficking. The encoded protein has similarity to yeast Sec23p component of COPII. COPII is the coat protein complex responsible for vesicle budding from the ER. The function of this gene product has been implicated in cargo selection and concentration. Multiple alternatively spliced transcript variants have been identified in this gene. [provided by RefSeq, Feb 2010]

SEC23B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026350617).

BP6

Variant 20-18542358-C-G is Benign according to our data. Variant chr20-18542358-C-G is described in ClinVar as [Benign]. Clinvar id is 95382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-18542358-C-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC23B	NM_006363.6 linkuse as main transcript	c.1467C>G	p.His489Gln	missense_variant	13/20	ENST00000650089.1	NP_006354.2	Q15437

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC23B	ENST00000650089.1 linkuse as main transcript	c.1467C>G	p.His489Gln	missense_variant	13/20		NM_006363.6	ENSP00000497473.1		Q15437

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

19043

AN:

152160

Hom.:

1302

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.159

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.160

Gnomad SAS

AF:

0.0411

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.118

Gnomad OTH

AF:

0.145

GnomAD3 exomes

AF:

0.128

AC:

32275

AN:

251452

Hom.:

2333

AF XY:

0.122

AC XY:

16586

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.207

Gnomad ASJ exome

AF:

0.144

Gnomad EAS exome

AF:

0.169

Gnomad SAS exome

AF:

0.0451

Gnomad FIN exome

AF:

0.129

Gnomad NFE exome

AF:

0.121

Gnomad OTH exome

AF:

0.128

GnomAD4 exome

AF:

0.114

AC:

167281

AN:

1461750

Hom.:

10323

Cov.:

AF XY:

0.112

AC XY:

81585

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.117

Gnomad4 AMR exome

AF:

0.204

Gnomad4 ASJ exome

AF:

0.149

Gnomad4 EAS exome

AF:

0.150

Gnomad4 SAS exome

AF:

0.0456

Gnomad4 FIN exome

AF:

0.128

Gnomad4 NFE exome

AF:

0.113

Gnomad4 OTH exome

AF:

0.114

GnomAD4 genome

AF:

0.125

AC:

19045

AN:

152278

Hom.:

1301

Cov.:

AF XY:

0.126

AC XY:

9368

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.114

Gnomad4 AMR

AF:

0.183

Gnomad4 ASJ

AF:

0.165

Gnomad4 EAS

AF:

0.160

Gnomad4 SAS

AF:

0.0412

Gnomad4 FIN

AF:

0.131

Gnomad4 NFE

AF:

0.118

Gnomad4 OTH

AF:

0.144

Alfa

AF:

0.110

Hom.:

792

Bravo

AF:

0.132

TwinsUK

AF:

0.118

AC:

439

ALSPAC

AF:

0.109

AC:

421

ESP6500AA

AF:

0.121

AC:

531

ESP6500EA

AF:

0.118

AC:

1012

ExAC

AF:

0.124

AC:

15100

Asia WGS

AF:

0.0990

AC:

344

AN:

3478

EpiCase

AF:

0.121

EpiControl

AF:

0.125

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 30, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 30, 2018	This variant is associated with the following publications: (PMID: 29300242, 29031773) -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 09, 2012	- -

Congenital dyserythropoietic anemia, type II

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

Congenital dyserythropoietic anemia, type II;C4225179:Cowden syndrome 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Cowden syndrome 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;T;T;.;T;T

Eigen

Benign

0.17

Eigen_PC

Benign

0.091

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.96

.;.;.;D;.;D

MetaRNN

Benign

0.0026

T;T;T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Pathogenic

3.2

M;M;M;.;M;M

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-7.1

D;D;D;.;.;D

REVEL

Uncertain

0.41

Sift

Uncertain

0.018

D;D;D;.;.;D

Sift4G

Uncertain

0.013

D;D;D;.;.;D

Polyphen

0.45

B;B;B;.;B;B

Vest4

0.24

MutPred

0.28

Gain of MoRF binding (P = 0.0941);Gain of MoRF binding (P = 0.0941);Gain of MoRF binding (P = 0.0941);.;Gain of MoRF binding (P = 0.0941);Gain of MoRF binding (P = 0.0941);

MPC

0.39

ClinPred

0.11

GERP RS

0.58

Varity_R

0.84

gMVP

0.75

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