rs4731970

Positions:

• chr7-133641849-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021807.4(EXOC4):​c.1514+11708C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,978 control chromosomes in the GnomAD database, including 14,509 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 0.42 (14509 hom., cov: 32)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOC4	NM_021807.4	c.1514+11708C>T		intron_variant		ENST00000253861.5	NP_068579.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOC4	ENST00000253861.5	c.1514+11708C>T		intron_variant		1	NM_021807.4	ENSP00000253861	P1

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64281 AN: 151860 Hom.: 14496 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.423 AC: 64328 AN: 151978 Hom.: 14509 Cov.: 32 AF XY: 0.431 AC XY: 31992 AN XY: 74274

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.544

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.416

Alfa AF: 0.425 Hom.: 6908

Bravo AF: 0.422

Asia WGS AF: 0.420 AC: 1463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs4731970; hg19: chr7-133326602;