rs3823572

Positions:

• chr7-133995848-G-A
• chr7-133995848-G-C

Variant summary

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

The NM_021807.4(EXOC4):​c.2207-1644G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,912 control chromosomes in the GnomAD database, including 21,148 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 0.51 (21148 hom., cov: 31)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOC4	NM_021807.4	c.2207-1644G>A		intron_variant		ENST00000253861.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOC4	ENST00000253861.5	c.2207-1644G>A		intron_variant		1	NM_021807.4	P1
EXOC4	ENST00000478265.1	n.453-1644G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77808 AN: 151794 Hom.: 21137 Cov.: 31

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.513 AC: 77865 AN: 151912 Hom.: 21148 Cov.: 31 AF XY: 0.512 AC XY: 38008 AN XY: 74264

Gnomad4 AFR AF: 0.678

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.509

Alfa AF: 0.460 Hom.: 21248

Bravo AF: 0.510

Asia WGS AF: 0.539 AC: 1870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.77
DANN	Benign	0.23

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: rs3823572; hg19: chr7-133680601;