Genetic Variant SEC24B:c.134-9_134-5dupCTTTT (chr4-109462891-G-GCTTTT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_006323.5(SEC24B):c.134-9_134-5dupCTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 1,577,082 control chromosomes in the GnomAD database, including 788,339 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 1.0 ( 76051 hom., cov: 0)

Exomes 𝑓: 1.0 ( 712288 hom. )

Consequence

SEC24B
NM_006323.5 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.100

Variant links:

Genes affected

SEC24B (HGNC:10704): (SEC24 homolog B, COPII coat complex component) The protein encoded by this gene is a member of the SEC24 subfamily of the SEC23/SEC24 family, which is involved in vesicle trafficking. The encoded protein is thought to be a cargo-binding component of the COPII vesicle, and is thought to be involved in the transport of secretory proteins from the endoplasmic reticulum to the Golgi apparatus. Mutations in this gene have been associated with neural tube defects, and are thought to be a result of a disruption in interactions with the protein encoded by the VANGL planar cell polarity protein 2 (VANGL2) gene. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

SEC24B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 4-109462891-G-GCTTTT is Benign according to our data. Variant chr4-109462891-G-GCTTTT is described in ClinVar as [Benign]. Clinvar id is 767969.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC24B	NM_006323.5 link	c.134-9_134-5dupCTTTT		splice_region_variant, intron_variant	Intron 1 of 23	ENST00000265175.5	NP_006314.2	O95487-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SEC24B	ENST00000265175.5 link	c.134-10_134-9insCTTTT	intron_variant	Intron 1 of 23	1	NM_006323.5	ENSP00000265175.4	O95487-1
SEC24B	ENST00000504968.6 link	c.227-10_227-9insCTTTT	intron_variant	Intron 2 of 24	1		ENSP00000428564.1	O95487-3
SEC24B	ENST00000399100.6 link	c.134-10_134-9insCTTTT	intron_variant	Intron 1 of 22	1		ENSP00000382051.2	O95487-2

Frequencies

GnomAD3 genomes

AF:

0.999

AC:

152065

AN:

152146

Hom.:

75992

Cov.:

show subpopulations

Gnomad AFR

AF:

0.998

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

1.00

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.998

GnomAD2 exomes

AF:

1.00

AC:

222593

AN:

222638

AF XY:

1.00

show subpopulations

Gnomad AFR exome

AF:

0.998

Gnomad AMR exome

AF:

1.00

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

AF:

1.00

AC:

1424697

AN:

1424818

Hom.:

712288

Cov.:

AF XY:

1.00

AC XY:

708468

AN XY:

708518

show subpopulations

Gnomad4 AFR exome

AF:

0.998

AC:

32449

AN:

32500

Gnomad4 AMR exome

AF:

1.00

AC:

41040

AN:

41058

Gnomad4 ASJ exome

AF:

1.00

AC:

24595

AN:

24596

Gnomad4 EAS exome

AF:

1.00

AC:

39490

AN:

39490

Gnomad4 SAS exome

AF:

1.00

AC:

82638

AN:

82644

Gnomad4 FIN exome

AF:

1.00

AC:

43280

AN:

43282

Gnomad4 NFE exome

AF:

1.00

AC:

1096371

AN:

1096410

Gnomad4 Remaining exome

AF:

1.00

AC:

59216

AN:

59220

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

21424

42848

64272

85696

107120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.999

AC:

152183

AN:

152264

Hom.:

76051

Cov.:

AF XY:

1.00

AC XY:

74416

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.998

AC:

0.998267

AN:

0.998267

Gnomad4 AMR

AF:

1.00

AC:

0.999869

AN:

0.999869

Gnomad4 ASJ

AF:

1.00

AC:

AN:

Gnomad4 EAS

AF:

1.00

AC:

AN:

Gnomad4 SAS

AF:

1.00

AC:

AN:

Gnomad4 FIN

AF:

1.00

AC:

AN:

Gnomad4 NFE

AF:

1.00

AC:

0.999956

AN:

0.999956

Gnomad4 OTH

AF:

0.998

AC:

0.998104

AN:

0.998104

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.999

Hom.:

12665

Asia WGS

AF:

0.999

AC:

3474

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 12, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over