rs2273525

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006363.6(SEC23B):c.1405-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0859 in 1,613,372 control chromosomes in the GnomAD database, including 8,525 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.096 ( 881 hom., cov: 33)

Exomes 𝑓: 0.085 ( 7644 hom. )

Consequence

SEC23B
NM_006363.6 splice_region, intron

Scores

Splicing: ADA: 0.0002003

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.395

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

congenital dyserythropoietic anemia type 2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Laboratory for Molecular Medicine, ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae)
Cowden disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Cowden syndrome 7
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
congenital dyserythropoietic anemia
Inheritance: AR Classification: LIMITED Submitted by: Genomics England PanelApp

SEC23B links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_006363.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 20-18542289-C-T is Benign according to our data. Variant chr20-18542289-C-T is described in ClinVar as Benign. ClinVar VariationId is 95381.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006363.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SEC23B	NM_006363.6	MANE Select	c.1405-7C>T	splice_region intron	N/A	NP_006354.2
SEC23B	NM_001172745.3		c.1405-7C>T	splice_region intron	N/A	NP_001166216.1	Q15437
SEC23B	NM_032985.6		c.1405-7C>T	splice_region intron	N/A	NP_116780.1	Q15437

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SEC23B	ENST00000650089.1	MANE Select	c.1405-7C>T	splice_region intron	N/A	ENSP00000497473.1	Q15437
SEC23B	ENST00000336714.8	TSL:1	c.1405-7C>T	splice_region intron	N/A	ENSP00000338844.3	Q15437
SEC23B	ENST00000377465.6	TSL:1	c.1405-7C>T	splice_region intron	N/A	ENSP00000366685.1	Q15437

Frequencies

GnomAD3 genomes

AF:

0.0960

AC:

14606

AN:

152074

Hom.:

875

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0967

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.103

Gnomad EAS

AF:

0.269

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.0987

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0692

Gnomad OTH

AF:

0.0988

GnomAD2 exomes

AF:

0.119

AC:

29796

AN:

251296

AF XY:

0.116

show subpopulations

Gnomad AFR exome

AF:

0.0992

Gnomad AMR exome

AF:

0.199

Gnomad ASJ exome

AF:

0.0975

Gnomad EAS exome

AF:

0.258

Gnomad FIN exome

AF:

0.0958

Gnomad NFE exome

AF:

0.0711

Gnomad OTH exome

AF:

0.106

GnomAD4 exome

AF:

0.0848

AC:

123973

AN:

1461178

Hom.:

7644

Cov.:

AF XY:

0.0860

AC XY:

62525

AN XY:

726916

show subpopulations

African (AFR)

AF:

0.0969

AC:

3242

AN:

33458

American (AMR)

AF:

0.193

AC:

8639

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0999

AC:

2610

AN:

26126

East Asian (EAS)

AF:

0.329

AC:

13077

AN:

39696

South Asian (SAS)

AF:

0.154

AC:

13300

AN:

86250

European-Finnish (FIN)

AF:

0.0953

AC:

5087

AN:

53354

Middle Eastern (MID)

AF:

0.0858

AC:

495

AN:

5768

European-Non Finnish (NFE)

AF:

0.0648

AC:

72021

AN:

1111426

Other (OTH)

AF:

0.0911

AC:

5502

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

5995

11990

17984

23979

29974

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2992

5984

8976

11968

14960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0962

AC:

14639

AN:

152194

Hom.:

881

Cov.:

AF XY:

0.101

AC XY:

7486

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0968

AC:

4018

AN:

41528

American (AMR)

AF:

0.136

AC:

2083

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

359

AN:

3470

East Asian (EAS)

AF:

0.269

AC:

1391

AN:

5164

South Asian (SAS)

AF:

0.159

AC:

766

AN:

4818

European-Finnish (FIN)

AF:

0.0987

AC:

1046

AN:

10594

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0692

AC:

4707

AN:

68016

Other (OTH)

AF:

0.104

AC:

220

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

646

1291

1937

2582

3228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

178

356

534

712

890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0808

Hom.:

1181

Bravo

AF:

0.101

Asia WGS

AF:

0.247

AC:

858

AN:

3478

EpiCase

AF:

0.0699

EpiControl

AF:

0.0731

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (3)

Congenital dyserythropoietic anemia, type II (1)

Congenital dyserythropoietic anemia, type II;C4225179:Cowden syndrome 7 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

4.7

(source)

DANN

Benign

0.73

PhyloP100

0.40

PromoterAI

-0.023

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00020

dbscSNV1_RF

Benign

0.0020

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over