7-133268228-C-G

Variant names:

• chr7-133268228-C-G
• rs1343697
• NM_021807.4:c.87-6754C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021807.4(EXOC4):​c.87-6754C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,158 control chromosomes in the GnomAD database, including 2,237 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 0.16 (2237 hom., cov: 32)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.722
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC4	NM_021807.4	c.87-6754C>G		intron_variant	Intron 1 of 17	ENST00000253861.5	NP_068579.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC4	ENST00000253861.5	c.87-6754C>G		intron_variant	Intron 1 of 17	1	NM_021807.4	ENSP00000253861.4

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23967 AN: 152040 Hom.: 2235 Cov.: 32

Gnomad AFR AF: 0.0723

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.00598

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.158 AC: 23976 AN: 152158 Hom.: 2237 Cov.: 32 AF XY: 0.155 AC XY: 11532 AN XY: 74348

African (AFR) AF: 0.0723 AC: 3002 AN: 41524

American (AMR) AF: 0.142 AC: 2169 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 716 AN: 3466

East Asian (EAS) AF: 0.00600 AC: 31 AN: 5168

South Asian (SAS) AF: 0.150 AC: 724 AN: 4824

European-Finnish (FIN) AF: 0.197 AC: 2079 AN: 10562

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14680 AN: 68002

Other (OTH) AF: 0.165 AC: 348 AN: 2114

Alfa AF: 0.0975 Hom.: 148

Bravo AF: 0.150

Asia WGS AF: 0.0710 AC: 249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.67
PhyloP100		-0.72
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: rs1343697; hg19: chr7-132952983;