rs13117307

Positions:

• chr4-55885574-C-T

Variant summary

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

The ENST00000381295.7(EXOC1):​c.1330+1646C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 151,970 control chromosomes in the GnomAD database, including 3,675 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 0.21 (3675 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: EXOC1 ENST00000381295.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.504

Genes affected

EXOC1 (HGNC:30380): (exocyst complex component 1) 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 the 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. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

RNU6-652P (HGNC:47615): (RNA, U6 small nuclear 652, pseudogene)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOC1	NM_001024924.2	c.1330+1646C>T		intron_variant		ENST00000381295.7	NP_001020095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOC1	ENST00000381295.7	c.1330+1646C>T		intron_variant		1	NM_001024924.2	ENSP00000370695	A1
RNU6-652P	ENST00000365488.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31868 AN: 151852 Hom.: 3674 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.213

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.210 AC: 31855 AN: 151970 Hom.: 3675 Cov.: 32 AF XY: 0.212 AC XY: 15761 AN XY: 74254

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.212

Alfa AF: 0.226 Hom.: 635

Bravo AF: 0.193

Asia WGS AF: 0.129 AC: 445 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.81
DANN	Benign	0.68

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: rs13117307; hg19: chr4-56751740;