7-133553847-G-T

Variant names:

• chr7-133553847-G-T
• rs12536963
• NM_021807.4:c.1417+73709G>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.1417+73709G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 152,034 control chromosomes in the GnomAD database, including 30,589 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 0.62 (30589 hom., cov: 32)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 3 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 (SAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021807.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC4	NM_021807.4	MANE Select	c.1417+73709G>T		intron	N/A	NP_068579.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC4	ENST00000253861.5	TSL:1 MANE Select	c.1417+73709G>T		intron	N/A	ENSP00000253861.4
	EXOC4	ENST00000850617.1		c.1417+73709G>T		intron	N/A	ENSP00000520904.1
	EXOC4	ENST00000479839.6	TSL:4	n.305+73709G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94597 AN: 151916 Hom.: 30567 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.642

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

GnomAD4 genome AF: 0.623 AC: 94658 AN: 152034 Hom.: 30589 Cov.: 32 AF XY: 0.628 AC XY: 46664 AN XY: 74330

African (AFR) AF: 0.438 AC: 18133 AN: 41424

American (AMR) AF: 0.699 AC: 10662 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2289 AN: 3468

East Asian (EAS) AF: 0.709 AC: 3676 AN: 5182

South Asian (SAS) AF: 0.728 AC: 3516 AN: 4828

European-Finnish (FIN) AF: 0.764 AC: 8083 AN: 10584

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.680 AC: 46213 AN: 67970

Other (OTH) AF: 0.643 AC: 1356 AN: 2110

Alfa AF: 0.598 Hom.: 3231

Bravo AF: 0.605

Asia WGS AF: 0.696 AC: 2419 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.25
DANN	Benign	0.49
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12536963; hg19: chr7-133238601;