7-133958268-CT-CTT

Variant summary

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

The NM_021807.4(EXOC4):c.2206+20208dup 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.455

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]

ACMG classification

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/exons	MANE	UniProt
EXOC4	NM_021807.4	c.2206+20208dup		intron_variant		ENST00000253861.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOC4	ENST00000253861.5	c.2206+20208dup		intron_variant		1	NM_021807.4	P1
EXOC4	ENST00000478265.1	n.452+20208dup		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.697 AC: 104531 AN: 150022 Hom.: 36772 Cov.: 0

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.: 0 AF XY: 0.701 AC XY: 51234 AN XY: 73134

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs5887652; hg19: chr7-133643021;