NM_021807.4:c.1183-22438T>C

Variant names:

• chr7-133452890-T-C
• rs10488165
• NM_021807.4:c.1183-22438T>C

Variant summary

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

The NM_021807.4(EXOC4):​c.1183-22438T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 151,958 control chromosomes in the GnomAD database, including 8,653 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 0.31 (8653 hom., cov: 30)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.948
• Publications: 9 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=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 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.1183-22438T>C		intron	N/A	NP_068579.3
	EXOC4	NM_001037126.2		c.1183-22438T>C		intron	N/A	NP_001032203.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC4	ENST00000253861.5	TSL:1 MANE Select	c.1183-22438T>C		intron	N/A	ENSP00000253861.4
	EXOC4	ENST00000462055.5	TSL:1	n.1190-22438T>C		intron	N/A
	EXOC4	ENST00000850617.1		c.1183-22438T>C		intron	N/A	ENSP00000520904.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46921 AN: 151838 Hom.: 8641 Cov.: 30

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.309 AC: 46948 AN: 151958 Hom.: 8653 Cov.: 30 AF XY: 0.317 AC XY: 23560 AN XY: 74254

African (AFR) AF: 0.113 AC: 4670 AN: 41486

American (AMR) AF: 0.467 AC: 7121 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1277 AN: 3468

East Asian (EAS) AF: 0.501 AC: 2581 AN: 5150

South Asian (SAS) AF: 0.281 AC: 1354 AN: 4816

European-Finnish (FIN) AF: 0.468 AC: 4938 AN: 10542

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23845 AN: 67924

Other (OTH) AF: 0.331 AC: 698 AN: 2110

Alfa AF: 0.343 Hom.: 16605

Bravo AF: 0.304

Asia WGS AF: 0.386 AC: 1343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	9.7
DANN	Benign	0.71
PhyloP100		0.95
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: rs10488165; hg19: chr7-133137644;