chr7-133363002-T-C

Position:

• chr7-133363002-T-C

Variant summary

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

The NM_021807.4(EXOC4):​c.1007+6429T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,104 control chromosomes in the GnomAD database, including 10,632 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 0.33 (10632 hom., cov: 32)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.897

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=-0.26).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOC4	NM_021807.4	c.1007+6429T>C		intron_variant		ENST00000253861.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOC4	ENST00000253861.5	c.1007+6429T>C		intron_variant		1	NM_021807.4	P1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50826 AN: 151986 Hom.: 10623 Cov.: 32

Gnomad AFR AF: 0.0912

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.334 AC: 50844 AN: 152104 Hom.: 10632 Cov.: 32 AF XY: 0.343 AC XY: 25517 AN XY: 74364

Gnomad4 AFR AF: 0.0910

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.343

Alfa AF: 0.346 Hom.: 4412

Bravo AF: 0.328

Asia WGS AF: 0.395 AC: 1375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	17
DANN	Benign	0.66

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: rs1149558; hg19: chr7-133047756;