chr7-133658675-C-T

Variant names:

• chr7-133658675-C-T
• rs763645
• NM_021807.4:c.1514+28534C>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.1514+28534C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,950 control chromosomes in the GnomAD database, including 14,854 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 0.43 (14854 hom., cov: 33)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.861
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC4	NM_021807.4	c.1514+28534C>T		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.1514+28534C>T		intron_variant	Intron 10 of 17	1	NM_021807.4	ENSP00000253861.4

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64952 AN: 151832 Hom.: 14840 Cov.: 33

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.428 AC: 64997 AN: 151950 Hom.: 14854 Cov.: 33 AF XY: 0.435 AC XY: 32302 AN XY: 74232

African (AFR) AF: 0.295 AC: 12210 AN: 41432

American (AMR) AF: 0.566 AC: 8631 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1742 AN: 3466

East Asian (EAS) AF: 0.547 AC: 2816 AN: 5146

South Asian (SAS) AF: 0.300 AC: 1441 AN: 4808

European-Finnish (FIN) AF: 0.563 AC: 5946 AN: 10562

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30774 AN: 67958

Other (OTH) AF: 0.421 AC: 889 AN: 2110

Alfa AF: 0.428 Hom.: 2763

Bravo AF: 0.427

Asia WGS AF: 0.420 AC: 1462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.48
DANN	Benign	0.76
PhyloP100		-0.86
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: rs763645; hg19: chr7-133343428;