7-133312478-A-C

Position:

• chr7-133312478-A-C

Variant summary

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

The NM_021807.4(EXOC4):​c.657-4806A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,100 control chromosomes in the GnomAD database, including 2,039 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 0.15 (2039 hom., cov: 32)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOC4	NM_021807.4	c.657-4806A>C		intron_variant		ENST00000253861.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOC4	ENST00000253861.5	c.657-4806A>C		intron_variant		1	NM_021807.4	P1
EXOC4	ENST00000462055.5	n.664-4806A>C		intron_variant, non_coding_transcript_variant		1
EXOC4	ENST00000393161.6	c.657-4806A>C		intron_variant		5
EXOC4	ENST00000486013.5	n.686-4806A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22832 AN: 151980 Hom.: 2037 Cov.: 32

Gnomad AFR AF: 0.0693

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.00538

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.150 AC: 22840 AN: 152100 Hom.: 2039 Cov.: 32 AF XY: 0.148 AC XY: 11037 AN XY: 74350

Gnomad4 AFR AF: 0.0693

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.00540

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.165

Alfa AF: 0.177 Hom.: 349

Bravo AF: 0.142

Asia WGS AF: 0.0720 AC: 250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.59
DANN	Benign	0.54

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: rs1922420; hg19: chr7-132997232;