rs7457999

Variant names:

• chr7-134063482-T-C
• rs7457999
• NM_021807.4:c.2688-809T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-134063482-T-C
• chr7-134063482-T-G

Variant summary

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

The NM_021807.4(EXOC4):​c.2688-809T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,082 control chromosomes in the GnomAD database, including 8,076 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 0.31 (8076 hom., cov: 32)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357
• Publications: 10 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC4	NM_021807.4	c.2688-809T>C		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.2688-809T>C		intron_variant	Intron 17 of 17	1	NM_021807.4	ENSP00000253861.4
EXOC4	ENST00000850617.1	c.2688-809T>C		intron_variant	Intron 17 of 19			ENSP00000520904.1
EXOC4	ENST00000459626.1	n.425-809T>C		intron_variant	Intron 1 of 1	3
EXOC4	ENST00000466000.1	n.236-809T>C		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47601 AN: 151966 Hom.: 8052 Cov.: 32

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.313 AC: 47674 AN: 152082 Hom.: 8076 Cov.: 32 AF XY: 0.315 AC XY: 23400 AN XY: 74382

African (AFR) AF: 0.444 AC: 18418 AN: 41440

American (AMR) AF: 0.347 AC: 5301 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 961 AN: 3466

East Asian (EAS) AF: 0.190 AC: 985 AN: 5180

South Asian (SAS) AF: 0.215 AC: 1035 AN: 4824

European-Finnish (FIN) AF: 0.314 AC: 3322 AN: 10580

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16694 AN: 67994

Other (OTH) AF: 0.302 AC: 639 AN: 2114

Alfa AF: 0.260 Hom.: 6934

Bravo AF: 0.324

Asia WGS AF: 0.212 AC: 740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.61
PhyloP100		-0.36
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: rs7457999; hg19: chr7-133748235;