NM_021807.4:c.1515-77410G>A

Variant names:

• chr7-133739915-G-A
• rs17167240
• NM_021807.4:c.1515-77410G>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.1515-77410G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,064 control chromosomes in the GnomAD database, including 4,953 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 0.22 (4953 hom., cov: 32)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.449
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC4	NM_021807.4	c.1515-77410G>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.1515-77410G>A		intron_variant	Intron 10 of 17	1	NM_021807.4	ENSP00000253861.4

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33635 AN: 151946 Hom.: 4943 Cov.: 32

Gnomad AFR AF: 0.0511

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.221 AC: 33655 AN: 152064 Hom.: 4953 Cov.: 32 AF XY: 0.229 AC XY: 17017 AN XY: 74302

African (AFR) AF: 0.0509 AC: 2115 AN: 41512

American (AMR) AF: 0.398 AC: 6066 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1039 AN: 3468

East Asian (EAS) AF: 0.449 AC: 2320 AN: 5162

South Asian (SAS) AF: 0.202 AC: 972 AN: 4822

European-Finnish (FIN) AF: 0.340 AC: 3593 AN: 10556

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16799 AN: 67976

Other (OTH) AF: 0.230 AC: 486 AN: 2112

Alfa AF: 0.247 Hom.: 6446

Bravo AF: 0.221

Asia WGS AF: 0.316 AC: 1097 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.0
DANN	Benign	0.38
PhyloP100		0.45
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: rs17167240; hg19: chr7-133424668;