7-133756033-T-G

Variant names:

• chr7-133756033-T-G
• rs6963221
• NM_021807.4:c.1515-61292T>G

Variant summary

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

The NM_021807.4(EXOC4):​c.1515-61292T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,006 control chromosomes in the GnomAD database, including 14,767 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 0.44 (14767 hom., cov: 31)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC4	NM_021807.4	c.1515-61292T>G		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.1515-61292T>G		intron_variant	Intron 10 of 17	1	NM_021807.4	ENSP00000253861.4

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66213 AN: 151888 Hom.: 14746 Cov.: 31

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.436 AC: 66271 AN: 152006 Hom.: 14767 Cov.: 31 AF XY: 0.434 AC XY: 32251 AN XY: 74278

African (AFR) AF: 0.498 AC: 20629 AN: 41450

American (AMR) AF: 0.329 AC: 5028 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1329 AN: 3466

East Asian (EAS) AF: 0.338 AC: 1741 AN: 5154

South Asian (SAS) AF: 0.533 AC: 2570 AN: 4824

European-Finnish (FIN) AF: 0.434 AC: 4579 AN: 10558

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.427 AC: 29035 AN: 67958

Other (OTH) AF: 0.441 AC: 930 AN: 2110

Alfa AF: 0.423 Hom.: 58143

Bravo AF: 0.424

Asia WGS AF: 0.445 AC: 1545 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.56
PhyloP100		-1.0
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: rs6963221; hg19: chr7-133440786;