7-133450753-A-T

Position:

• chr7-133450753-A-T

Variant summary

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

The NM_021807.4(EXOC4):​c.1183-24575A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,206 control chromosomes in the GnomAD database, including 5,374 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 0.26 (5374 hom., cov: 33)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOC4	NM_021807.4	c.1183-24575A>T		intron_variant		ENST00000253861.5	NP_068579.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOC4	ENST00000253861.5	c.1183-24575A>T		intron_variant		1	NM_021807.4	ENSP00000253861	P1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38860 AN: 152088 Hom.: 5375 Cov.: 33

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.255 AC: 38874 AN: 152206 Hom.: 5374 Cov.: 33 AF XY: 0.253 AC XY: 18847 AN XY: 74404

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.275

Alfa AF: 0.147 Hom.: 282

Bravo AF: 0.246

Asia WGS AF: 0.326 AC: 1130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.78

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: rs13241123; hg19: chr7-133135507;