rs958404

Positions:

• chr7-133912433-A-C
• chr7-133912433-A-G

Variant summary

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

The NM_021807.4(EXOC4):​c.1872-5150A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 152,042 control chromosomes in the GnomAD database, including 17,980 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 0.47 (17980 hom., cov: 33)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.366

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=-0.58).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOC4	NM_021807.4	c.1872-5150A>C		intron_variant		ENST00000253861.5	NP_068579.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOC4	ENST00000253861.5	c.1872-5150A>C		intron_variant		1	NM_021807.4	ENSP00000253861	P1
EXOC4	ENST00000460346.5	n.628-5150A>C		intron_variant, non_coding_transcript_variant		4
EXOC4	ENST00000472020.1	n.271-5150A>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71062 AN: 151924 Hom.: 17952 Cov.: 33

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.468 AC: 71144 AN: 152042 Hom.: 17980 Cov.: 33 AF XY: 0.465 AC XY: 34553 AN XY: 74344

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.485

Alfa AF: 0.423 Hom.: 7261

Bravo AF: 0.475

Asia WGS AF: 0.553 AC: 1919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.7
DANN	Benign	0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs958404; hg19: chr7-133597186;