rs10249912

Variant names:

• chr7-134053360-C-T
• rs10249912
• NM_021807.4:c.2688-10931C>T

Variant summary

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

The NM_021807.4(EXOC4):​c.2688-10931C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 151,910 control chromosomes in the GnomAD database, including 2,840 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 0.18 (2840 hom., cov: 32)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC4	NM_021807.4	c.2688-10931C>T		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.2688-10931C>T		intron_variant	Intron 17 of 17	1	NM_021807.4	ENSP00000253861.4
EXOC4	ENST00000850617.1	c.2688-10931C>T		intron_variant	Intron 17 of 19			ENSP00000520904.1
EXOC4	ENST00000459626.1	n.425-10931C>T		intron_variant	Intron 1 of 1	3
EXOC4	ENST00000466000.1	n.236-10931C>T		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27100 AN: 151800 Hom.: 2833 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0920

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.179 AC: 27149 AN: 151910 Hom.: 2840 Cov.: 32 AF XY: 0.174 AC XY: 12912 AN XY: 74260

African (AFR) AF: 0.280 AC: 11588 AN: 41396

American (AMR) AF: 0.175 AC: 2666 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 555 AN: 3466

East Asian (EAS) AF: 0.169 AC: 875 AN: 5166

South Asian (SAS) AF: 0.129 AC: 624 AN: 4822

European-Finnish (FIN) AF: 0.0920 AC: 967 AN: 10514

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9285 AN: 67964

Other (OTH) AF: 0.208 AC: 438 AN: 2102

Alfa AF: 0.160 Hom.: 5549

Bravo AF: 0.192

Asia WGS AF: 0.163 AC: 565 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	4.9
DANN	Benign	0.72
PhyloP100		-0.095
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: rs10249912; hg19: chr7-133738113;