7-133569350-C-T

Variant names:

• chr7-133569350-C-T
• rs10954418
• NM_021807.4:c.1418-60695C>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.1418-60695C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 151,940 control chromosomes in the GnomAD database, including 30,439 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 (30439 hom., cov: 31)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.709 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.1418-60695C>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.1418-60695C>T		intron	N/A	ENSP00000253861.4
	EXOC4	ENST00000850617.1		c.1418-60695C>T		intron	N/A	ENSP00000520904.1
	EXOC4	ENST00000479839.6	TSL:4	n.306-60695C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94406 AN: 151820 Hom.: 30415 Cov.: 31

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.642

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

GnomAD4 genome AF: 0.622 AC: 94469 AN: 151940 Hom.: 30439 Cov.: 31 AF XY: 0.627 AC XY: 46565 AN XY: 74248

African (AFR) AF: 0.441 AC: 18259 AN: 41392

American (AMR) AF: 0.701 AC: 10701 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2294 AN: 3468

East Asian (EAS) AF: 0.710 AC: 3670 AN: 5170

South Asian (SAS) AF: 0.729 AC: 3504 AN: 4806

European-Finnish (FIN) AF: 0.750 AC: 7923 AN: 10568

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46029 AN: 67942

Other (OTH) AF: 0.643 AC: 1360 AN: 2116

Alfa AF: 0.655 Hom.: 14828

Bravo AF: 0.606

Asia WGS AF: 0.698 AC: 2425 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.53
DANN	Benign	0.62
PhyloP100		-0.20
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: rs10954418; hg19: chr7-133254104;