rs6954842

Positions:

• chr7-133603379-A-G
• chr7-133603379-A-T

Variant summary

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

The NM_021807.4(EXOC4):​c.1418-26666A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,094 control chromosomes in the GnomAD database, including 30,956 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 0.63 (30956 hom., cov: 33)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460

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 (SAS) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOC4	NM_021807.4	c.1418-26666A>G		intron_variant		ENST00000253861.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOC4	ENST00000253861.5	c.1418-26666A>G		intron_variant		1	NM_021807.4	P1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95152 AN: 151976 Hom.: 30937 Cov.: 33

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.645

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

GnomAD4 genome AF: 0.626 AC: 95209 AN: 152094 Hom.: 30956 Cov.: 33 AF XY: 0.632 AC XY: 47006 AN XY: 74372

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.664

Gnomad4 EAS AF: 0.714

Gnomad4 SAS AF: 0.720

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.682

Gnomad4 OTH AF: 0.643

Alfa AF: 0.602 Hom.: 3266

Bravo AF: 0.608

Asia WGS AF: 0.699 AC: 2430 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.51

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: rs6954842; hg19: chr7-133288133;