7-133996348-T-C

Variant names:

• chr7-133996348-T-C
• rs7792010
• NM_021807.4:c.2207-1144T>C

Variant summary

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

The NM_021807.4(EXOC4):​c.2207-1144T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,026 control chromosomes in the GnomAD database, including 8,750 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 0.33 (8750 hom., cov: 32)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 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.2207-1144T>C		intron	N/A	NP_068579.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC4	ENST00000253861.5	TSL:1 MANE Select	c.2207-1144T>C		intron	N/A	ENSP00000253861.4	Q96A65-1
	EXOC4	ENST00000852803.1		c.2342-1144T>C		intron	N/A	ENSP00000522862.1
	EXOC4	ENST00000933610.1		c.2258-1144T>C		intron	N/A	ENSP00000603669.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50429 AN: 151906 Hom.: 8740 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.332 AC: 50484 AN: 152026 Hom.: 8750 Cov.: 32 AF XY: 0.333 AC XY: 24736 AN XY: 74302

African (AFR) AF: 0.409 AC: 16942 AN: 41450

American (AMR) AF: 0.256 AC: 3920 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 810 AN: 3466

East Asian (EAS) AF: 0.292 AC: 1510 AN: 5166

South Asian (SAS) AF: 0.408 AC: 1962 AN: 4810

European-Finnish (FIN) AF: 0.357 AC: 3773 AN: 10554

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20554 AN: 67978

Other (OTH) AF: 0.342 AC: 722 AN: 2112

Alfa AF: 0.308 Hom.: 24080

Bravo AF: 0.324

Asia WGS AF: 0.353 AC: 1221 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.6
DANN	Benign	0.71
PhyloP100		-0.046
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: rs7792010; hg19: chr7-133681101;