rs11770757

chr7-134063193-G-Achr7-134063193-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_021807.4(EXOC4):c.2688-1098G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0325 in 152,206 control chromosomes in the GnomAD database, including 153 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 0.032 (153 hom., cov: 32)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.717

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=-0.86).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0325 (4943/152206) while in subpopulation NFE AF= 0.044 (2996/68014). AF 95% confidence interval is 0.0427. There are 153 homozygotes in gnomad4. There are 2590 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 153 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOC4	NM_021807.4	c.2688-1098G>A		intron_variant		ENST00000253861.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOC4	ENST00000253861.5	c.2688-1098G>A		intron_variant		1	NM_021807.4	P1
EXOC4	ENST00000459626.1	n.425-1098G>A		intron_variant, non_coding_transcript_variant		3
EXOC4	ENST00000466000.1	n.236-1098G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0325 AC: 4945 AN: 152088 Hom.: 153 Cov.: 32

Gnomad AFR AF: 0.00664

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0234

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0441

Gnomad OTH AF: 0.0283

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

GnomAD4 genome AF: 0.0325 AC: 4943 AN: 152206 Hom.: 153 Cov.: 32 AF XY: 0.0348 AC XY: 2590 AN XY: 74402

Gnomad4 AFR AF: 0.00662

Gnomad4 AMR AF: 0.0233

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00456

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.0440

Gnomad4 OTH AF: 0.0280

Alfa AF: 0.0329 Hom.: 57

Bravo AF: 0.0255

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	5.7
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: rs11770757; hg19: chr7-133747946;