chr7-133725116-A-G

Position:

• chr7-133725116-A-G

Variant summary

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

The NM_021807.4(EXOC4):​c.1515-92209A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 152,196 control chromosomes in the GnomAD database, including 58,052 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 0.87 (58052 hom., cov: 32)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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=-0.91).
• 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	Protein	UniProt
EXOC4	NM_021807.4	c.1515-92209A>G		intron_variant		ENST00000253861.5	NP_068579.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOC4	ENST00000253861.5	c.1515-92209A>G		intron_variant		1	NM_021807.4	ENSP00000253861	P1

Frequencies

GnomAD3 genomes AF: 0.869 AC: 132147 AN: 152078 Hom.: 58014 Cov.: 32

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.922

Gnomad ASJ AF: 0.934

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.920

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.890

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

GnomAD4 genome AF: 0.869 AC: 132235 AN: 152196 Hom.: 58052 Cov.: 32 AF XY: 0.870 AC XY: 64732 AN XY: 74422

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.922

Gnomad4 ASJ AF: 0.934

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.920

Gnomad4 FIN AF: 0.873

Gnomad4 NFE AF: 0.921

Gnomad4 OTH AF: 0.891

Alfa AF: 0.914 Hom.: 81574

Bravo AF: 0.868

Asia WGS AF: 0.937 AC: 3258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.59
DANN	Benign	0.58

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: rs1362736; hg19: chr7-133409869;