rs191103191

Variant names:

• chr20-18507935-T-G
• rs191103191
• ENST00000336714.8:c.-70T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000336714.8(SEC23B):​c.-70T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00623 in 152,718 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0062 (13 hom., cov: 34)
  • Exomes 𝑓: 0.0025 (0 hom.)
• Consequence: SEC23B ENST00000336714.8 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.301
• Publications: 0 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency = 0.0833 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000336714.8. 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_032986.5		c.-15+266T>G		intron	N/A	NP_116781.1	Q15437
	SEC23B	NM_006363.6	MANE Select	c.-52T>G		upstream_gene	N/A	NP_006354.2
	SEC23B	NM_001172745.3		c.-377T>G		upstream_gene	N/A	NP_001166216.1	Q15437

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC23B	ENST00000336714.8	TSL:1	c.-70T>G		5_prime_UTR	Exon 1 of 20	ENSP00000338844.3	Q15437
	SEC23B	ENST00000262544.6	TSL:5	c.-110T>G		5_prime_UTR	Exon 1 of 20	ENSP00000262544.2	Q15437
	SEC23B	ENST00000874272.1		c.-277T>G		5_prime_UTR	Exon 1 of 21	ENSP00000544331.1

Frequencies

GnomAD3 genomes AF: 0.00609 AC: 927 AN: 152192 Hom.: 11 Cov.: 34

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.00245 AC: 1 AN: 408 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 304

African (AFR) AF: 0.0833 AC: 1 AN: 12

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AF: 0.00 AC: 0 AN: 6

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 344

Other (OTH) AF: 0.00 AC: 0 AN: 22

GnomAD4 genome AF: 0.00624 AC: 951 AN: 152310 Hom.: 13 Cov.: 34 AF XY: 0.00634 AC XY: 472 AN XY: 74474

African (AFR) AF: 0.0219 AC: 911 AN: 41576

American (AMR) AF: 0.00203 AC: 31 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00332 AC: 7 AN: 2110

Alfa AF: 0.00592 Hom.: 1

Bravo AF: 0.00740

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Congenital dyserythropoietic anemia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.3
DANN	Benign	0.43
PhyloP100		-0.30
PromoterAI		-0.088	Neutral
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs191103191; hg19: chr20-18488579;