rs142180765

Variant names:

• chr20-18560747-GAT-G
• rs142180765
• NM_006363.6:c.*9_*10delTA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_006363.6(SEC23B):​c.*9_*10delTA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,605,784 control chromosomes in the GnomAD database, including 80 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (37 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (43 hom.)
• Consequence: SEC23B NM_006363.6 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0280
• 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 -16 ACMG points.

• BP6: Variant 20-18560747-GAT-G is Benign according to our data. Variant chr20-18560747-GAT-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 195501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0109 (1666/152326) while in subpopulation AFR AF = 0.0384 (1597/41568). AF 95% confidence interval is 0.0369. There are 37 homozygotes in GnomAd4. There are 821 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 37 AR,AD gene

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.*9_*10delTA		3_prime_UTR	Exon 20 of 20	NP_006354.2
	SEC23B	NM_001172745.3		c.*9_*10delTA		3_prime_UTR	Exon 20 of 20	NP_001166216.1	Q15437
	SEC23B	NM_032985.6		c.*9_*10delTA		3_prime_UTR	Exon 20 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.*9_*10delTA		3_prime_UTR	Exon 20 of 20	ENSP00000497473.1	Q15437
	SEC23B	ENST00000336714.8	TSL:1	c.*9_*10delTA		3_prime_UTR	Exon 20 of 20	ENSP00000338844.3	Q15437
	SEC23B	ENST00000377465.6	TSL:1	c.*9_*10delTA		3_prime_UTR	Exon 20 of 20	ENSP00000366685.1	Q15437

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1642 AN: 152208 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.0379

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

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: 0.0000294

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00292 AC: 733 AN: 251424 AF XY: 0.00210

Gnomad AFR exome AF: 0.0391

Gnomad AMR exome AF: 0.00223

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00114 AC: 1664 AN: 1453458 Hom.: 43 AF XY: 0.00101 AC XY: 730 AN XY: 723732

African (AFR) AF: 0.0414 AC: 1376 AN: 33260

American (AMR) AF: 0.00213 AC: 95 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.000105 AC: 9 AN: 86066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00330 AC: 19 AN: 5758

European-Non Finnish (NFE) AF: 0.0000290 AC: 32 AN: 1104400

Other (OTH) AF: 0.00221 AC: 133 AN: 60110

GnomAD4 genome AF: 0.0109 AC: 1666 AN: 152326 Hom.: 37 Cov.: 32 AF XY: 0.0110 AC XY: 821 AN XY: 74482

African (AFR) AF: 0.0384 AC: 1597 AN: 41568

American (AMR) AF: 0.00346 AC: 53 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68040

Other (OTH) AF: 0.00614 AC: 13 AN: 2116

Alfa AF: 0.00562 Hom.: 2

Bravo AF: 0.0126

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Congenital dyserythropoietic anemia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.028
Mutation Taster		=100/0	polymorphism

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: rs142180765; hg19: chr20-18541391;