rs12155007

Variant names:

• chr7-133900676-G-C
• rs12155007
• NM_021807.4:c.1871+4941G>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.1871+4941G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 152,178 control chromosomes in the GnomAD database, including 163 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 0.038 (163 hom., cov: 32)
• Consequence: EXOC4 NM_021807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.190
• Publications: 1 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 (NFE) allele frequency at 95% confidence interval = 0.0545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC4	NM_021807.4	c.1871+4941G>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.1871+4941G>C		intron_variant	Intron 12 of 17	1	NM_021807.4	ENSP00000253861.4
EXOC4	ENST00000850617.1	c.1871+4941G>C		intron_variant	Intron 12 of 19			ENSP00000520904.1
EXOC4	ENST00000460346.5	n.627+4941G>C		intron_variant	Intron 4 of 4	4
EXOC4	ENST00000472020.1	n.270+4941G>C		intron_variant	Intron 2 of 3	4

Frequencies

GnomAD3 genomes AF: 0.0381 AC: 5791 AN: 152060 Hom.: 163 Cov.: 32

Gnomad AFR AF: 0.0112

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.0347

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0415

Gnomad FIN AF: 0.0384

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0560

Gnomad OTH AF: 0.0412

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

GnomAD4 genome AF: 0.0380 AC: 5790 AN: 152178 Hom.: 163 Cov.: 32 AF XY: 0.0372 AC XY: 2769 AN XY: 74384

African (AFR) AF: 0.0111 AC: 462 AN: 41536

American (AMR) AF: 0.0346 AC: 529 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.0418 AC: 201 AN: 4810

European-Finnish (FIN) AF: 0.0384 AC: 407 AN: 10608

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0560 AC: 3806 AN: 67988

Other (OTH) AF: 0.0412 AC: 87 AN: 2110

Alfa AF: 0.0460 Hom.: 32

Bravo AF: 0.0375

Asia WGS AF: 0.0190 AC: 66 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	5.8
DANN	Benign	0.47
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism

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: rs12155007; hg19: chr7-133585429; COSMIC: COSV99552090; COSMIC: COSV99552090;