7-133436098-C-T

Variant names:

• chr7-133436098-C-T
• rs718656
• NM_021807.4:c.1183-39230C>T

Variant summary

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

The NM_021807.4(EXOC4):​c.1183-39230C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 149,576 control chromosomes in the GnomAD database, including 45,390 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 0.77 (45390 hom., cov: 26)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.684
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC4	NM_021807.4	c.1183-39230C>T		intron_variant	Intron 7 of 17	ENST00000253861.5	NP_068579.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC4	ENST00000253861.5	c.1183-39230C>T		intron_variant	Intron 7 of 17	1	NM_021807.4	ENSP00000253861.4

Frequencies

GnomAD3 genomes AF: 0.774 AC: 115744 AN: 149490 Hom.: 45367 Cov.: 26

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.901

Gnomad FIN AF: 0.852

Gnomad MID AF: 0.806

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.790

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

GnomAD4 genome AF: 0.774 AC: 115796 AN: 149576 Hom.: 45390 Cov.: 26 AF XY: 0.779 AC XY: 56669 AN XY: 72788

African (AFR) AF: 0.652 AC: 26464 AN: 40564

American (AMR) AF: 0.826 AC: 12446 AN: 15076

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2688 AN: 3470

East Asian (EAS) AF: 0.948 AC: 4845 AN: 5110

South Asian (SAS) AF: 0.901 AC: 4278 AN: 4748

European-Finnish (FIN) AF: 0.852 AC: 8244 AN: 9678

Middle Eastern (MID) AF: 0.800 AC: 232 AN: 290

European-Non Finnish (NFE) AF: 0.802 AC: 54257 AN: 67652

Other (OTH) AF: 0.792 AC: 1654 AN: 2088

Alfa AF: 0.780 Hom.: 5737

Bravo AF: 0.764

Asia WGS AF: 0.901 AC: 3130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.5
DANN	Benign	0.56
PhyloP100		0.68
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: rs718656; hg19: chr7-133120852;