rs9649047

chr7-133748761-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021807.4(EXOC4):c.1515-68564C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 152,202 control chromosomes in the GnomAD database, including 59,583 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.88 (59583 hom., cov: 31)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOC4	NM_021807.4	c.1515-68564C>G		intron_variant		ENST00000253861.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOC4	ENST00000253861.5	c.1515-68564C>G		intron_variant		1	NM_021807.4	P1

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134313 AN: 152084 Hom.: 59536 Cov.: 31

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.928

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.866

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.905

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

GnomAD4 genome AF: 0.883 AC: 134416 AN: 152202 Hom.: 59583 Cov.: 31 AF XY: 0.884 AC XY: 65758 AN XY: 74412

Gnomad4 AFR AF: 0.801

Gnomad4 AMR AF: 0.928

Gnomad4 ASJ AF: 0.928

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.919

Gnomad4 FIN AF: 0.869

Gnomad4 NFE AF: 0.911

Gnomad4 OTH AF: 0.907

Alfa AF: 0.895 Hom.: 7580

Bravo AF: 0.885

Asia WGS AF: 0.941 AC: 3270 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	8.7
Dann	Benign	0.53

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: rs9649047; hg19: chr7-133433514;