rs2953617

Variant names:

• chr7-133989347-T-A
• rs2953617
• NM_021807.4:c.2207-8145T>A

Your query was ambiguous. Multiple possible variants found:

• chr7-133989347-T-A
• chr7-133989347-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.2207-8145T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,974 control chromosomes in the GnomAD database, including 18,973 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 0.48 (18973 hom., cov: 31)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC4	NM_021807.4	c.2207-8145T>A		intron_variant	Intron 14 of 17	ENST00000253861.5	NP_068579.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC4	ENST00000253861.5	c.2207-8145T>A		intron_variant	Intron 14 of 17	1	NM_021807.4	ENSP00000253861.4
EXOC4	ENST00000850617.1	c.2207-8145T>A		intron_variant	Intron 14 of 19			ENSP00000520904.1
EXOC4	ENST00000478265.1	n.453-8145T>A		intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73648 AN: 151854 Hom.: 18965 Cov.: 31

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.485 AC: 73698 AN: 151974 Hom.: 18973 Cov.: 31 AF XY: 0.485 AC XY: 36008 AN XY: 74284

African (AFR) AF: 0.646 AC: 26766 AN: 41436

American (AMR) AF: 0.363 AC: 5552 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1209 AN: 3470

East Asian (EAS) AF: 0.467 AC: 2416 AN: 5172

South Asian (SAS) AF: 0.597 AC: 2878 AN: 4822

European-Finnish (FIN) AF: 0.425 AC: 4478 AN: 10526

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.425 AC: 28866 AN: 67968

Other (OTH) AF: 0.484 AC: 1020 AN: 2106

Alfa AF: 0.459 Hom.: 2056

Bravo AF: 0.483

Asia WGS AF: 0.537 AC: 1861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.51
PhyloP100		0.048
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: rs2953617; hg19: chr7-133674100;