Genetic Variant EXOC4:c.2206+20208dupT (chr7-133958268-C-CT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_021807.4(EXOC4):c.2206+20208dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.70 ( 36800 hom., cov: 0)

Consequence

EXOC4
NM_021807.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.455

Variant links:

Genes affected

EXOC4 (HGNC:30389): (exocyst complex component 4) The protein encoded by this gene is a component of the exocyst complex, a multiple protein complex essential for targeting exocytic vesicles to specific docking sites on the plasma membrane. Though best characterized in yeast, the component proteins and functions of exocyst complex have been demonstrated to be highly conserved in higher eukaryotes. At least eight components of the exocyst complex, including this protein, are found to interact with the actin cytoskeletal remodeling and vesicle transport machinery. The complex is also essential for the biogenesis of epithelial cell surface polarity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

EXOC4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC4	NM_021807.4 link	c.2206+20208dupT		intron_variant	Intron 14 of 17	ENST00000253861.5	NP_068579.3	Q96A65-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC4	ENST00000253861.5 link	c.2206+20199_2206+20200insT		intron_variant	Intron 14 of 17	1	NM_021807.4	ENSP00000253861.4		Q96A65-1
EXOC4	ENST00000478265.1 link	n.452+20199_452+20200insT		intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.697

AC:

104531

AN:

150022

Hom.:

36772

Cov.:

show subpopulations

Gnomad AFR

AF:

0.717

Gnomad AMI

AF:

0.579

Gnomad AMR

AF:

0.761

Gnomad ASJ

AF:

0.652

Gnomad EAS

AF:

0.907

Gnomad SAS

AF:

0.778

Gnomad FIN

AF:

0.680

Gnomad MID

AF:

0.655

Gnomad NFE

AF:

0.654

Gnomad OTH

AF:

0.712

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.697

AC:

104604

AN:

150122

Hom.:

36800

Cov.:

AF XY:

0.701

AC XY:

51234

AN XY:

73134

show subpopulations

Gnomad4 AFR

AF:

0.717

Gnomad4 AMR

AF:

0.762

Gnomad4 ASJ

AF:

0.652

Gnomad4 EAS

AF:

0.908

Gnomad4 SAS

AF:

0.778

Gnomad4 FIN

AF:

0.680

Gnomad4 NFE

AF:

0.654

Gnomad4 OTH

AF:

0.714

Asia WGS

AF:

0.822

AC:

2831

AN:

3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing