20-18548589-T-A

Variant names:

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.1744-20T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 1,608,286 control chromosomes in the GnomAD database, including 125,909 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9551 hom., cov: 33)

Exomes 𝑓: 0.40 ( 116358 hom. )

Consequence

SEC23B
NM_006363.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 3.50

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=-0.78).

BP6

Variant 20-18548589-T-A is Benign according to our data. Variant chr20-18548589-T-A is described in ClinVar as Benign. ClinVar VariationId is 95385.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.442 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.1744-20T>A	intron	N/A	NP_006354.2
SEC23B	NM_001172745.3		c.1744-20T>A	intron	N/A	NP_001166216.1	Q15437
SEC23B	NM_032985.6		c.1744-20T>A	intron	N/A	NP_116780.1	Q15437

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SEC23B	ENST00000650089.1	MANE Select	c.1744-20T>A	intron	N/A	ENSP00000497473.1	Q15437
SEC23B	ENST00000336714.8	TSL:1	c.1744-20T>A	intron	N/A	ENSP00000338844.3	Q15437
SEC23B	ENST00000377465.6	TSL:1	c.1744-20T>A	intron	N/A	ENSP00000366685.1	Q15437

Frequencies

GnomAD3 genomes

AF:

0.341

AC:

51797

AN:

152010

Hom.:

9552

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.325

Gnomad AMR

AF:

0.314

Gnomad ASJ

AF:

0.212

Gnomad EAS

AF:

0.419

Gnomad SAS

AF:

0.456

Gnomad FIN

AF:

0.442

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.404

Gnomad OTH

AF:

0.302

GnomAD2 exomes

AF:

0.376

AC:

94042

AN:

250294

AF XY:

0.385

show subpopulations

Gnomad AFR exome

AF:

0.204

Gnomad AMR exome

AF:

0.290

Gnomad ASJ exome

AF:

0.231

Gnomad EAS exome

AF:

0.427

Gnomad FIN exome

AF:

0.434

Gnomad NFE exome

AF:

0.403

Gnomad OTH exome

AF:

0.365

GnomAD4 exome

AF:

0.395

AC:

575785

AN:

1456156

Hom.:

116358

Cov.:

AF XY:

0.398

AC XY:

288238

AN XY:

724686

show subpopulations

African (AFR)

AF:

0.208

AC:

6941

AN:

33410

American (AMR)

AF:

0.292

AC:

13028

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

5721

AN:

26100

East Asian (EAS)

AF:

0.362

AC:

14341

AN:

39664

South Asian (SAS)

AF:

0.443

AC:

38154

AN:

86080

European-Finnish (FIN)

AF:

0.438

AC:

23335

AN:

53312

Middle Eastern (MID)

AF:

0.294

AC:

1696

AN:

5760

European-Non Finnish (NFE)

AF:

0.406

AC:

449537

AN:

1106996

Other (OTH)

AF:

0.383

AC:

23032

AN:

60194

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

15212

30424

45637

60849

76061

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13734

27468

41202

54936

68670

<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:

0.341

AC:

51807

AN:

152130

Hom.:

9551

Cov.:

AF XY:

0.345

AC XY:

25661

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.210

AC:

8707

AN:

41506

American (AMR)

AF:

0.314

AC:

4802

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.212

AC:

737

AN:

3470

East Asian (EAS)

AF:

0.418

AC:

2166

AN:

5178

South Asian (SAS)

AF:

0.458

AC:

2207

AN:

4820

European-Finnish (FIN)

AF:

0.442

AC:

4664

AN:

10562

Middle Eastern (MID)

AF:

0.320

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.404

AC:

27498

AN:

67994

Other (OTH)

AF:

0.301

AC:

636

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1712

3424

5136

6848

8560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

516

1032

1548

2064

2580

<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:

0.364

Hom.:

1994

Bravo

AF:

0.321

Asia WGS

AF:

0.403

AC:

1399

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

not provided (3)

Congenital dyserythropoietic anemia, type II (1)

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

Cowden syndrome 7 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.3

(source)

DANN

Benign

0.54

PhyloP100

3.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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