chr7-134052277-G-T

Variant names:

• chr7-134052277-G-T
• rs6955114
• NM_021807.4:c.2688-12014G>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.2688-12014G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,934 control chromosomes in the GnomAD database, including 13,912 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 0.42 (13912 hom., cov: 32)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC4	NM_021807.4	c.2688-12014G>T		intron_variant	Intron 17 of 17	ENST00000253861.5	NP_068579.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC4	ENST00000253861.5	c.2688-12014G>T		intron_variant	Intron 17 of 17	1	NM_021807.4	ENSP00000253861.4
EXOC4	ENST00000850617.1	c.2688-12014G>T		intron_variant	Intron 17 of 19			ENSP00000520904.1
EXOC4	ENST00000459626.1	n.425-12014G>T		intron_variant	Intron 1 of 1	3
EXOC4	ENST00000466000.1	n.236-12014G>T		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63438 AN: 151816 Hom.: 13881 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.418 AC: 63521 AN: 151934 Hom.: 13912 Cov.: 32 AF XY: 0.421 AC XY: 31243 AN XY: 74232

African (AFR) AF: 0.459 AC: 19012 AN: 41404

American (AMR) AF: 0.551 AC: 8414 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1443 AN: 3470

East Asian (EAS) AF: 0.608 AC: 3139 AN: 5164

South Asian (SAS) AF: 0.353 AC: 1701 AN: 4820

European-Finnish (FIN) AF: 0.396 AC: 4172 AN: 10546

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.358 AC: 24359 AN: 67948

Other (OTH) AF: 0.458 AC: 965 AN: 2108

Alfa AF: 0.394 Hom.: 35176

Bravo AF: 0.439

Asia WGS AF: 0.501 AC: 1738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.69
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6955114; hg19: chr7-133737030;