chr20-18508110-G-C

Variant names:

• chr20-18508110-G-C
• rs2281576
• ENST00000377465.6:c.-202G>C

Variant summary

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

The NM_001172745.3(SEC23B):​c.-202G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.83 in 152,188 control chromosomes in the GnomAD database, including 53,587 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (53564 hom., cov: 31)
  • Exomes 𝑓: 0.91 (23 hom.)
• Consequence: SEC23B NM_001172745.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.71
• Publications: 5 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: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, G2P, 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=-1.01).
• BP6: Variant 20-18508110-G-C is Benign according to our data. Variant chr20-18508110-G-C is described in ClinVar as Benign. ClinVar VariationId is 1281680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172745.3. 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.-15+138G>C		intron	N/A	NP_006354.2
	SEC23B	NM_001172745.3		c.-202G>C		5_prime_UTR	Exon 1 of 20	NP_001166216.1	Q15437
	SEC23B	NM_032985.6		c.-15+120G>C		intron	N/A	NP_116780.1	Q15437

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC23B	ENST00000377465.6	TSL:1	c.-202G>C		5_prime_UTR	Exon 1 of 20	ENSP00000366685.1	Q15437
	SEC23B	ENST00000650089.1	MANE Select	c.-15+138G>C		intron	N/A	ENSP00000497473.1	Q15437
	SEC23B	ENST00000336714.8	TSL:1	c.-15+120G>C		intron	N/A	ENSP00000338844.3	Q15437

Frequencies

GnomAD3 genomes AF: 0.831 AC: 126257 AN: 152016 Hom.: 53548 Cov.: 31

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.827

Gnomad ASJ AF: 0.880

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.927

Gnomad OTH AF: 0.847

GnomAD4 exome AF: 0.907 AC: 49 AN: 54 Hom.: 23 Cov.: 0 AF XY: 0.913 AC XY: 42 AN XY: 46

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.957 AC: 44 AN: 46

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.830 AC: 126323 AN: 152134 Hom.: 53564 Cov.: 31 AF XY: 0.829 AC XY: 61636 AN XY: 74362

African (AFR) AF: 0.657 AC: 27237 AN: 41486

American (AMR) AF: 0.826 AC: 12639 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.880 AC: 3054 AN: 3470

East Asian (EAS) AF: 0.729 AC: 3745 AN: 5134

South Asian (SAS) AF: 0.853 AC: 4107 AN: 4814

European-Finnish (FIN) AF: 0.901 AC: 9552 AN: 10602

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.927 AC: 63058 AN: 68012

Other (OTH) AF: 0.842 AC: 1779 AN: 2112

Alfa AF: 0.865 Hom.: 3372

Bravo AF: 0.813

Asia WGS AF: 0.747 AC: 2595 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.61
DANN	Benign	0.48
PhyloP100		-2.7
PromoterAI		0.060	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2281576; hg19: chr20-18488754;