rs10246346

Variant names:

• chr7-134080568-A-G
• rs10246346
• XR_007060531.1:n.17903T>C

Variant summary

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

The XR_007060531.1(LOC105375514):​n.17903T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 151,828 control chromosomes in the GnomAD database, including 5,430 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 0.22 (5430 hom., cov: 31)
• Consequence: LOC105375514 XR_007060531.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440
• Publications: 2 publications found

Genes affected

LOC105375514 (HGNC:):

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 = 0.461 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000727227.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000294998	ENST00000727227.1		n.78+6155A>G		intron	N/A
	ENSG00000295018	ENST00000727385.1		n.170-3438T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32730 AN: 151708 Hom.: 5408 Cov.: 31

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.0736

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0923

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.216 AC: 32800 AN: 151828 Hom.: 5430 Cov.: 31 AF XY: 0.211 AC XY: 15672 AN XY: 74230

African (AFR) AF: 0.467 AC: 19278 AN: 41294

American (AMR) AF: 0.166 AC: 2531 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 495 AN: 3470

East Asian (EAS) AF: 0.171 AC: 879 AN: 5144

South Asian (SAS) AF: 0.124 AC: 599 AN: 4814

European-Finnish (FIN) AF: 0.0923 AC: 975 AN: 10568

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7435 AN: 67978

Other (OTH) AF: 0.224 AC: 471 AN: 2104

Alfa AF: 0.139 Hom.: 1057

Bravo AF: 0.236

Asia WGS AF: 0.163 AC: 564 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	3.6
DANN	Benign	0.75
PhyloP100		-0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10246346; hg19: chr7-133765321;