20-18530812-A-G

Variant names:

• chr20-18530812-A-G
• rs6081189
• NM_006363.6:c.1233+9A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006363.6(SEC23B):​c.1233+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.983 in 1,604,196 control chromosomes in the GnomAD database, including 777,450 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (65577 hom., cov: 29)
  • Exomes 𝑓: 0.99 (711873 hom.)
• Consequence: SEC23B NM_006363.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.177
• Publications: 8 publications found

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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, G2P, PanelApp Australia, Laboratory for Molecular Medicine
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 20-18530812-A-G is Benign according to our data. Variant chr20-18530812-A-G is described in ClinVar as Benign. ClinVar VariationId is 95379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC23B	NM_006363.6	MANE Select	c.1233+9A>G		intron	N/A	NP_006354.2
	SEC23B	NM_001172745.3		c.1233+9A>G		intron	N/A	NP_001166216.1	Q15437
	SEC23B	NM_032985.6		c.1233+9A>G		intron	N/A	NP_116780.1	Q15437

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC23B	ENST00000650089.1	MANE Select	c.1233+9A>G		intron	N/A	ENSP00000497473.1	Q15437
	SEC23B	ENST00000336714.8	TSL:1	c.1233+9A>G		intron	N/A	ENSP00000338844.3	Q15437
	SEC23B	ENST00000377465.6	TSL:1	c.1233+9A>G		intron	N/A	ENSP00000366685.1	Q15437

Frequencies

GnomAD3 genomes AF: 0.924 AC: 139915 AN: 151404 Hom.: 65547 Cov.: 29

Gnomad AFR AF: 0.746

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.961

Gnomad ASJ AF: 0.983

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.998

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.996

Gnomad OTH AF: 0.944

GnomAD2 exomes AF: 0.978 AC: 241250 AN: 246626 AF XY: 0.983

Gnomad AFR exome AF: 0.743

Gnomad AMR exome AF: 0.982

Gnomad ASJ exome AF: 0.982

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.996

Gnomad OTH exome AF: 0.984

GnomAD4 exome AF: 0.989 AC: 1437042 AN: 1452684 Hom.: 711873 Cov.: 29 AF XY: 0.990 AC XY: 716190 AN XY: 723238

African (AFR) AF: 0.745 AC: 24595 AN: 33026

American (AMR) AF: 0.981 AC: 43649 AN: 44490

Ashkenazi Jewish (ASJ) AF: 0.982 AC: 25567 AN: 26036

East Asian (EAS) AF: 1.00 AC: 39619 AN: 39622

South Asian (SAS) AF: 0.997 AC: 85555 AN: 85788

European-Finnish (FIN) AF: 1.00 AC: 53067 AN: 53078

Middle Eastern (MID) AF: 0.967 AC: 5452 AN: 5638

European-Non Finnish (NFE) AF: 0.996 AC: 1100912 AN: 1105022

Other (OTH) AF: 0.977 AC: 58626 AN: 59984

GnomAD4 genome AF: 0.924 AC: 139995 AN: 151512 Hom.: 65577 Cov.: 29 AF XY: 0.927 AC XY: 68584 AN XY: 74016

African (AFR) AF: 0.746 AC: 30795 AN: 41266

American (AMR) AF: 0.961 AC: 14671 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.983 AC: 3409 AN: 3468

East Asian (EAS) AF: 1.00 AC: 5104 AN: 5104

South Asian (SAS) AF: 0.998 AC: 4792 AN: 4804

European-Finnish (FIN) AF: 1.00 AC: 10338 AN: 10340

Middle Eastern (MID) AF: 0.973 AC: 286 AN: 294

European-Non Finnish (NFE) AF: 0.996 AC: 67700 AN: 67952

Other (OTH) AF: 0.945 AC: 1988 AN: 2104

Alfa AF: 0.970 Hom.: 23754

Bravo AF: 0.912

Asia WGS AF: 0.982 AC: 3364 AN: 3426

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	not provided (3)
-	-	2	Congenital dyserythropoietic anemia, type II (2)
-	-	1	Congenital dyserythropoietic anemia, type II;C4225179:Cowden syndrome 7 (1)
-	-	1	Cowden syndrome 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.8
DANN	Benign	0.62
PhyloP100		0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs6081189; hg19: chr20-18511456;