rs10262862

Positions:

• chr7-133271279-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.87-3703C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 151,952 control chromosomes in the GnomAD database, including 36,286 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 0.67 (36286 hom., cov: 31)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOC4	NM_021807.4	c.87-3703C>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.87-3703C>T		intron_variant		1	NM_021807.4	ENSP00000253861	P1

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101926 AN: 151834 Hom.: 36238 Cov.: 31

Gnomad AFR AF: 0.910

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.671 AC: 102027 AN: 151952 Hom.: 36286 Cov.: 31 AF XY: 0.663 AC XY: 49232 AN XY: 74270

Gnomad4 AFR AF: 0.910

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.715

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.608

Gnomad4 OTH AF: 0.663

Alfa AF: 0.664 Hom.: 3324

Bravo AF: 0.677

Asia WGS AF: 0.601 AC: 2090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.76

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: rs10262862; hg19: chr7-132956034;