17-76081416-G-C

Variant names:

• chr17-76081416-G-C
• rs8836
• NM_001013839.4:c.*2232C>G

Variant summary

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

The NM_001013839.4(EXOC7):​c.*2232C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 1,613,742 control chromosomes in the GnomAD database, including 277,561 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 0.44 (18228 hom., cov: 33)
  • Exomes 𝑓: 0.59 (259333 hom.)
• Consequence: EXOC7 NM_001013839.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00

Genes affected

EXOC7 (HGNC:23214): (exocyst complex component 7) The protein encoded by this gene is a component of the exocyst complex. The exocyst complex plays a critical role in vesicular trafficking and the secretory pathway by targeting post-Golgi vesicles to the plasma membrane. The encoded protein is required for assembly of the exocyst complex and docking of the complex to the plasma membrane. The encoded protein may also play a role in pre-mRNA splicing through interactions with pre-mRNA-processing factor 19. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 4. [provided by RefSeq, Nov 2011]

ZACN (HGNC:29504): (zinc activated ion channel) LGICZ1 is a zinc-activated ligand-gated ion channel that defines a new subgroup of the cysteine-loop superfamily of ligand-gated ion channels (Davies et al., 2003 [PubMed 12381728]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC7	NM_001013839.4	c.*2232C>G		3_prime_UTR_variant	Exon 19 of 19	ENST00000589210.6	NP_001013861.1
ZACN	NM_180990.4	c.669+14G>C		intron_variant	Intron 6 of 8	ENST00000334586.10	NP_851321.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC7	ENST00000589210	c.*2232C>G		3_prime_UTR_variant	Exon 19 of 19	1	NM_001013839.4	ENSP00000468404.1
ZACN	ENST00000334586.10	c.669+14G>C		intron_variant	Intron 6 of 8	1	NM_180990.4	ENSP00000334854.5

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67341 AN: 152080 Hom.: 18225 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.449

GnomAD2 exomes AF: 0.538 AC: 134915 AN: 250844 AF XY: 0.557

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.399

Gnomad ASJ exome AF: 0.562

Gnomad EAS exome AF: 0.468

Gnomad FIN exome AF: 0.596

Gnomad NFE exome AF: 0.602

Gnomad OTH exome AF: 0.550

GnomAD4 exome AF: 0.588 AC: 859713 AN: 1461544 Hom.: 259333 Cov.: 73 AF XY: 0.593 AC XY: 431169 AN XY: 727078

Gnomad4 AFR exome AF: 0.0993 AC: 3324 AN: 33480

Gnomad4 AMR exome AF: 0.400 AC: 17901 AN: 44720

Gnomad4 ASJ exome AF: 0.559 AC: 14612 AN: 26124

Gnomad4 EAS exome AF: 0.469 AC: 18628 AN: 39700

Gnomad4 SAS exome AF: 0.677 AC: 58405 AN: 86242

Gnomad4 FIN exome AF: 0.600 AC: 31917 AN: 53222

Gnomad4 NFE exome AF: 0.610 AC: 677935 AN: 1111900

Gnomad4 Remaining exome AF: 0.561 AC: 33867 AN: 60388

GnomAD4 genome AF: 0.442 AC: 67343 AN: 152198 Hom.: 18228 Cov.: 33 AF XY: 0.444 AC XY: 33027 AN XY: 74400

Gnomad4 AFR AF: 0.124 AC: 0.123694 AN: 0.123694

Gnomad4 AMR AF: 0.391 AC: 0.391353 AN: 0.391353

Gnomad4 ASJ AF: 0.548 AC: 0.54755 AN: 0.54755

Gnomad4 EAS AF: 0.487 AC: 0.487219 AN: 0.487219

Gnomad4 SAS AF: 0.689 AC: 0.688691 AN: 0.688691

Gnomad4 FIN AF: 0.593 AC: 0.592788 AN: 0.592788

Gnomad4 NFE AF: 0.599 AC: 0.598717 AN: 0.598717

Gnomad4 OTH AF: 0.448 AC: 0.44839 AN: 0.44839

Alfa AF: 0.454 Hom.: 2582

Bravo AF: 0.408

Asia WGS AF: 0.534 AC: 1853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.1
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Mutation Taster		=22/78	disease causing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8836; hg19: chr17-74077497; COSMIC: COSV58035750; COSMIC: COSV58035750;