rs11772444

Variant names:

• chr7-133769121-G-A
• rs11772444
• NM_021807.4:c.1515-48204G>A

Variant summary

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

The NM_021807.4(EXOC4):​c.1515-48204G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 151,986 control chromosomes in the GnomAD database, including 1,648 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 0.12 (1648 hom., cov: 33)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240
• Publications: 6 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]

LOC124901749 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC4	NM_021807.4	c.1515-48204G>A		intron_variant	Intron 10 of 17	ENST00000253861.5	NP_068579.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC4	ENST00000253861.5	c.1515-48204G>A		intron_variant	Intron 10 of 17	1	NM_021807.4	ENSP00000253861.4

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18836 AN: 151868 Hom.: 1648 Cov.: 33

Gnomad AFR AF: 0.0326

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0849

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.124 AC: 18829 AN: 151986 Hom.: 1648 Cov.: 33 AF XY: 0.122 AC XY: 9044 AN XY: 74268

African (AFR) AF: 0.0325 AC: 1351 AN: 41508

American (AMR) AF: 0.105 AC: 1594 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 726 AN: 3464

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5170

South Asian (SAS) AF: 0.0850 AC: 409 AN: 4814

European-Finnish (FIN) AF: 0.146 AC: 1548 AN: 10580

Middle Eastern (MID) AF: 0.154 AC: 45 AN: 292

European-Non Finnish (NFE) AF: 0.187 AC: 12676 AN: 67918

Other (OTH) AF: 0.123 AC: 258 AN: 2100

Alfa AF: 0.167 Hom.: 1159

Bravo AF: 0.118

Asia WGS AF: 0.0410 AC: 145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.48
PhyloP100		-0.24
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: rs11772444; hg19: chr7-133453874;