rs7262532

Variant names:

• chr20-18554303-G-T
• rs7262532
• NM_006363.6:c.2061G>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_006363.6(SEC23B):​c.2061G>T​(p.Leu687Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00584 in 1,614,108 control chromosomes in the GnomAD database, including 390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (194 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (196 hom.)
• Consequence: SEC23B NM_006363.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.199
• Publications: 2 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 20-18554303-G-T is Benign according to our data. Variant chr20-18554303-G-T is described in ClinVar as Benign. ClinVar VariationId is 95386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.199 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0992 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.2061G>T	p.Leu687Leu	synonymous	Exon 18 of 20	NP_006354.2
	SEC23B	NM_001172745.3		c.2061G>T	p.Leu687Leu	synonymous	Exon 18 of 20	NP_001166216.1	Q15437
	SEC23B	NM_032985.6		c.2061G>T	p.Leu687Leu	synonymous	Exon 18 of 20	NP_116780.1	Q15437

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC23B	ENST00000650089.1	MANE Select	c.2061G>T	p.Leu687Leu	synonymous	Exon 18 of 20	ENSP00000497473.1	Q15437
	SEC23B	ENST00000336714.8	TSL:1	c.2061G>T	p.Leu687Leu	synonymous	Exon 18 of 20	ENSP00000338844.3	Q15437
	SEC23B	ENST00000377465.6	TSL:1	c.2061G>T	p.Leu687Leu	synonymous	Exon 18 of 20	ENSP00000366685.1	Q15437

Frequencies

GnomAD3 genomes AF: 0.0298 AC: 4536 AN: 152102 Hom.: 192 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.0177

GnomAD2 exomes AF: 0.00831 AC: 2089 AN: 251472 AF XY: 0.00589

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.00717

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000571

Gnomad OTH exome AF: 0.00651

GnomAD4 exome AF: 0.00334 AC: 4876 AN: 1461888 Hom.: 196 Cov.: 32 AF XY: 0.00296 AC XY: 2154 AN XY: 727246

African (AFR) AF: 0.105 AC: 3499 AN: 33480

American (AMR) AF: 0.00747 AC: 334 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000301 AC: 26 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00867 AC: 50 AN: 5768

European-Non Finnish (NFE) AF: 0.000433 AC: 482 AN: 1112006

Other (OTH) AF: 0.00803 AC: 485 AN: 60396

GnomAD4 genome AF: 0.0299 AC: 4546 AN: 152220 Hom.: 194 Cov.: 32 AF XY: 0.0288 AC XY: 2147 AN XY: 74424

African (AFR) AF: 0.102 AC: 4228 AN: 41528

American (AMR) AF: 0.0149 AC: 228 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000720 AC: 49 AN: 68022

Other (OTH) AF: 0.0175 AC: 37 AN: 2112

Alfa AF: 0.0177 Hom.: 91

Bravo AF: 0.0345

Asia WGS AF: 0.00375 AC: 14 AN: 3478

EpiCase AF: 0.000763

EpiControl AF: 0.000711

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	4.8
DANN	Benign	0.73
PhyloP100		0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=95/5	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: rs7262532; hg19: chr20-18534947; COSMIC: COSV52721457;