rs748754

Variant names:

• chr7-133824316-G-A
• rs748754
• NM_021807.4:c.1734+6772G>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.1734+6772G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,518 control chromosomes in the GnomAD database, including 6,770 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 0.29 (6770 hom., cov: 29)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 1 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]

LOC101928861 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC4	NM_021807.4	c.1734+6772G>A		intron_variant	Intron 11 of 17	ENST00000253861.5	NP_068579.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC4	ENST00000253861.5	c.1734+6772G>A		intron_variant	Intron 11 of 17	1	NM_021807.4	ENSP00000253861.4

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44369 AN: 151400 Hom.: 6753 Cov.: 29

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.293 AC: 44421 AN: 151518 Hom.: 6770 Cov.: 29 AF XY: 0.293 AC XY: 21684 AN XY: 74032

African (AFR) AF: 0.354 AC: 14636 AN: 41334

American (AMR) AF: 0.213 AC: 3247 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 800 AN: 3464

East Asian (EAS) AF: 0.301 AC: 1528 AN: 5076

South Asian (SAS) AF: 0.429 AC: 2050 AN: 4782

European-Finnish (FIN) AF: 0.265 AC: 2786 AN: 10498

Middle Eastern (MID) AF: 0.259 AC: 75 AN: 290

European-Non Finnish (NFE) AF: 0.272 AC: 18436 AN: 67852

Other (OTH) AF: 0.318 AC: 666 AN: 2092

Alfa AF: 0.283 Hom.: 780

Bravo AF: 0.288

Asia WGS AF: 0.368 AC: 1277 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	0.17
DANN	Benign	0.81
PhyloP100		-1.9
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: rs748754; hg19: chr7-133509069;