7-133959025-T-G

Variant names:

• chr7-133959025-T-G
• rs2971970
• NM_021807.4:c.2206+20956T>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.2206+20956T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 152,226 control chromosomes in the GnomAD database, including 55,947 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 (55947 hom., cov: 32)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.314
• Publications: 8 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 (AFR) allele frequency at 95% confidence interval = 0.953 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC4	NM_021807.4	MANE Select	c.2206+20956T>G		intron	N/A	NP_068579.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC4	ENST00000253861.5	TSL:1 MANE Select	c.2206+20956T>G		intron	N/A	ENSP00000253861.4
	EXOC4	ENST00000850617.1		c.2206+20956T>G		intron	N/A	ENSP00000520904.1
	EXOC4	ENST00000478265.1	TSL:4	n.452+20956T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.853 AC: 129787 AN: 152108 Hom.: 55882 Cov.: 32

Gnomad AFR AF: 0.961

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.889

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.849

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

GnomAD4 genome AF: 0.853 AC: 129912 AN: 152226 Hom.: 55947 Cov.: 32 AF XY: 0.856 AC XY: 63691 AN XY: 74412

African (AFR) AF: 0.961 AC: 39915 AN: 41538

American (AMR) AF: 0.863 AC: 13193 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2620 AN: 3470

East Asian (EAS) AF: 0.915 AC: 4730 AN: 5168

South Asian (SAS) AF: 0.889 AC: 4296 AN: 4834

European-Finnish (FIN) AF: 0.842 AC: 8930 AN: 10602

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.787 AC: 53538 AN: 68004

Other (OTH) AF: 0.851 AC: 1797 AN: 2112

Alfa AF: 0.809 Hom.: 25279

Bravo AF: 0.859

Asia WGS AF: 0.918 AC: 3191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.43
PhyloP100		-0.31
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: rs2971970; hg19: chr7-133643778;