7-133481415-G-T

Variant names:

• chr7-133481415-G-T
• rs6971417
• NM_021807.4:c.1417+1277G>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.1417+1277G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.85 in 152,184 control chromosomes in the GnomAD database, including 55,371 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 0.85 (55371 hom., cov: 32)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131
• Publications: 3 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]

LOC124901748 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021807.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC4	NM_021807.4	MANE Select	c.1417+1277G>T		intron	N/A	NP_068579.3
	EXOC4	NM_001037126.2		c.1417+1277G>T		intron	N/A	NP_001032203.1	Q96A65-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC4	ENST00000253861.5	TSL:1 MANE Select	c.1417+1277G>T		intron	N/A	ENSP00000253861.4	Q96A65-1
	EXOC4	ENST00000852803.1		c.1417+1277G>T		intron	N/A	ENSP00000522862.1
	EXOC4	ENST00000933610.1		c.1468+1277G>T		intron	N/A	ENSP00000603669.1

Frequencies

GnomAD3 genomes AF: 0.850 AC: 129311 AN: 152066 Hom.: 55317 Cov.: 32

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.777

Gnomad EAS AF: 0.948

Gnomad SAS AF: 0.904

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.838

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.845

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

GnomAD4 genome AF: 0.850 AC: 129423 AN: 152184 Hom.: 55371 Cov.: 32 AF XY: 0.852 AC XY: 63404 AN XY: 74386

African (AFR) AF: 0.914 AC: 37975 AN: 41532

American (AMR) AF: 0.856 AC: 13087 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.777 AC: 2698 AN: 3472

East Asian (EAS) AF: 0.949 AC: 4914 AN: 5178

South Asian (SAS) AF: 0.905 AC: 4358 AN: 4818

European-Finnish (FIN) AF: 0.850 AC: 8996 AN: 10578

Middle Eastern (MID) AF: 0.832 AC: 243 AN: 292

European-Non Finnish (NFE) AF: 0.804 AC: 54665 AN: 67998

Other (OTH) AF: 0.846 AC: 1789 AN: 2114

Alfa AF: 0.835 Hom.: 6622

Bravo AF: 0.853

Asia WGS AF: 0.920 AC: 3198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.49
PhyloP100		0.13
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: rs6971417; hg19: chr7-133166169;