rs17167267

Variant names:

• chr7-133784356-G-A
• rs17167267
• NM_021807.4:c.1515-32969G>A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_021807.4(EXOC4):​c.1515-32969G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,048 control chromosomes in the GnomAD database, including 1,210 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 0.11 (1210 hom., cov: 32)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC4	NM_021807.4	c.1515-32969G>A		intron_variant	Intron 10 of 17	ENST00000253861.5	NP_068579.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC4	ENST00000253861.5	c.1515-32969G>A		intron_variant	Intron 10 of 17	1	NM_021807.4	ENSP00000253861.4

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17305 AN: 151928 Hom.: 1203 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0794

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.0807

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.0885

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0845

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.114 AC: 17332 AN: 152048 Hom.: 1210 Cov.: 32 AF XY: 0.115 AC XY: 8540 AN XY: 74314

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.0794

Gnomad4 ASJ AF: 0.0657

Gnomad4 EAS AF: 0.0807

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.0885

Gnomad4 NFE AF: 0.0846

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0889 Hom.: 612

Bravo AF: 0.115

Asia WGS AF: 0.130 AC: 449 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs17167267; hg19: chr7-133469109;