chr7-133942683-C-T

Variant names:

• chr7-133942683-C-T
• rs4266574
• NM_021807.4:c.2206+4614C>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.2206+4614C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,010 control chromosomes in the GnomAD database, including 4,967 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 (4967 hom., cov: 31)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.285
• 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]

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 = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC4	NM_021807.4	c.2206+4614C>T		intron_variant	Intron 14 of 17	ENST00000253861.5	NP_068579.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC4	ENST00000253861.5	c.2206+4614C>T		intron_variant	Intron 14 of 17	1	NM_021807.4	ENSP00000253861.4
EXOC4	ENST00000850617.1	c.2206+4614C>T		intron_variant	Intron 14 of 19			ENSP00000520904.1
EXOC4	ENST00000478265.1	n.452+4614C>T		intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33882 AN: 151892 Hom.: 4960 Cov.: 31

Gnomad AFR AF: 0.0571

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.223 AC: 33897 AN: 152010 Hom.: 4967 Cov.: 31 AF XY: 0.230 AC XY: 17114 AN XY: 74296

African (AFR) AF: 0.0569 AC: 2362 AN: 41488

American (AMR) AF: 0.406 AC: 6203 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1099 AN: 3468

East Asian (EAS) AF: 0.437 AC: 2251 AN: 5156

South Asian (SAS) AF: 0.187 AC: 900 AN: 4810

European-Finnish (FIN) AF: 0.346 AC: 3649 AN: 10560

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

European-Non Finnish (NFE) AF: 0.246 AC: 16721 AN: 67942

Other (OTH) AF: 0.236 AC: 497 AN: 2110

Alfa AF: 0.241 Hom.: 15957

Bravo AF: 0.224

Asia WGS AF: 0.306 AC: 1063 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	0.56
DANN	Benign	0.83
PhyloP100		0.28
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: rs4266574; hg19: chr7-133627436;