7-133914774-T-C

Variant names:

• chr7-133914774-T-C
• rs6963032
• NM_021807.4:c.1872-2809T>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.1872-2809T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,028 control chromosomes in the GnomAD database, including 17,872 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 0.47 (17872 hom., cov: 33)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204
• Publications: 2 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 = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC4	NM_021807.4	c.1872-2809T>C		intron_variant	Intron 12 of 17	ENST00000253861.5	NP_068579.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC4	ENST00000253861.5	c.1872-2809T>C		intron_variant	Intron 12 of 17	1	NM_021807.4	ENSP00000253861.4
EXOC4	ENST00000850617.1	c.1872-2809T>C		intron_variant	Intron 12 of 19			ENSP00000520904.1
EXOC4	ENST00000460346.5	n.628-2809T>C		intron_variant	Intron 4 of 4	4
EXOC4	ENST00000472020.1	n.271-2809T>C		intron_variant	Intron 2 of 3	4

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70896 AN: 151910 Hom.: 17844 Cov.: 33

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.467 AC: 70978 AN: 152028 Hom.: 17872 Cov.: 33 AF XY: 0.464 AC XY: 34449 AN XY: 74288

African (AFR) AF: 0.654 AC: 27097 AN: 41458

American (AMR) AF: 0.349 AC: 5340 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1162 AN: 3468

East Asian (EAS) AF: 0.465 AC: 2407 AN: 5172

South Asian (SAS) AF: 0.619 AC: 2984 AN: 4820

European-Finnish (FIN) AF: 0.339 AC: 3578 AN: 10558

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26897 AN: 67940

Other (OTH) AF: 0.485 AC: 1025 AN: 2114

Alfa AF: 0.443 Hom.: 2040

Bravo AF: 0.473

Asia WGS AF: 0.551 AC: 1910 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	2.0
DANN	Benign	0.74
PhyloP100		0.20
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: rs6963032; hg19: chr7-133599527;