7-133574761-C-T

Variant names:

• chr7-133574761-C-T
• rs10755879
• NM_021807.4:c.1418-55284C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021807.4(EXOC4):​c.1418-55284C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 152,168 control chromosomes in the GnomAD database, including 56,551 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 0.86 (56551 hom., cov: 33)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC4	NM_021807.4	c.1418-55284C>T		intron_variant	Intron 9 of 17	ENST00000253861.5	NP_068579.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC4	ENST00000253861.5	c.1418-55284C>T		intron_variant	Intron 9 of 17	1	NM_021807.4	ENSP00000253861.4

Frequencies

GnomAD3 genomes AF: 0.861 AC: 130927 AN: 152050 Hom.: 56515 Cov.: 33

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.912

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.863

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

GnomAD4 genome AF: 0.861 AC: 131017 AN: 152168 Hom.: 56551 Cov.: 33 AF XY: 0.861 AC XY: 64097 AN XY: 74402

African (AFR) AF: 0.820 AC: 33987 AN: 41470

American (AMR) AF: 0.884 AC: 13519 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.886 AC: 3074 AN: 3470

East Asian (EAS) AF: 0.765 AC: 3947 AN: 5162

South Asian (SAS) AF: 0.833 AC: 4014 AN: 4820

European-Finnish (FIN) AF: 0.912 AC: 9681 AN: 10610

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.882 AC: 59967 AN: 68026

Other (OTH) AF: 0.861 AC: 1820 AN: 2114

Alfa AF: 0.849 Hom.: 2976

Bravo AF: 0.856

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.53
DANN	Benign	0.32
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10755879; hg19: chr7-133259515;