rs2178689

Variant names:

• chr7-133268943-A-T
• rs2178689
• NM_021807.4:c.87-6039A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021807.4(EXOC4):​c.87-6039A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 152,200 control chromosomes in the GnomAD database, including 58,104 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 (58104 hom., cov: 32)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC4	NM_021807.4	c.87-6039A>T		intron_variant	Intron 1 of 17	ENST00000253861.5	NP_068579.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC4	ENST00000253861.5	c.87-6039A>T		intron_variant	Intron 1 of 17	1	NM_021807.4	ENSP00000253861.4

Frequencies

GnomAD3 genomes AF: 0.870 AC: 132276 AN: 152082 Hom.: 58040 Cov.: 32

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.889

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.911

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.870

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

GnomAD4 genome AF: 0.870 AC: 132400 AN: 152200 Hom.: 58104 Cov.: 32 AF XY: 0.871 AC XY: 64853 AN XY: 74416

African (AFR) AF: 0.967 AC: 40192 AN: 41556

American (AMR) AF: 0.889 AC: 13599 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2694 AN: 3460

East Asian (EAS) AF: 0.998 AC: 5176 AN: 5184

South Asian (SAS) AF: 0.911 AC: 4397 AN: 4826

European-Finnish (FIN) AF: 0.822 AC: 8698 AN: 10578

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.807 AC: 54883 AN: 67988

Other (OTH) AF: 0.871 AC: 1840 AN: 2112

Alfa AF: 0.846 Hom.: 6825

Bravo AF: 0.877

Asia WGS AF: 0.958 AC: 3327 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	14
DANN	Benign	0.87
PhyloP100		-0.065
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2178689; hg19: chr7-132953698;