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
• Publications: 18 publications found

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013839.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC7	NM_001013839.4	MANE Select	c.*2232C>G		3_prime_UTR	Exon 19 of 19	NP_001013861.1	Q9UPT5-1
	ZACN	NM_180990.4	MANE Select	c.669+14G>C		intron	N/A	NP_851321.2	Q401N2-1
	EXOC7	NM_001145297.4		c.*2232C>G		3_prime_UTR	Exon 20 of 20	NP_001138769.1	Q9UPT5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC7	ENST00000589210.6	TSL:1 MANE Select	c.*2232C>G		3_prime_UTR	Exon 19 of 19	ENSP00000468404.1	Q9UPT5-1
	ZACN	ENST00000334586.10	TSL:1 MANE Select	c.669+14G>C		intron	N/A	ENSP00000334854.5	Q401N2-1
	EXOC7	ENST00000945913.1		c.*2232C>G		3_prime_UTR	Exon 18 of 18	ENSP00000615972.1

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

African (AFR) AF: 0.0993 AC: 3324 AN: 33480

American (AMR) AF: 0.400 AC: 17901 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 14612 AN: 26124

East Asian (EAS) AF: 0.469 AC: 18628 AN: 39700

South Asian (SAS) AF: 0.677 AC: 58405 AN: 86242

European-Finnish (FIN) AF: 0.600 AC: 31917 AN: 53222

Middle Eastern (MID) AF: 0.542 AC: 3124 AN: 5768

European-Non Finnish (NFE) AF: 0.610 AC: 677935 AN: 1111900

Other (OTH) 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

African (AFR) AF: 0.124 AC: 5140 AN: 41554

American (AMR) AF: 0.391 AC: 5983 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1900 AN: 3470

East Asian (EAS) AF: 0.487 AC: 2516 AN: 5164

South Asian (SAS) AF: 0.689 AC: 3325 AN: 4828

European-Finnish (FIN) AF: 0.593 AC: 6280 AN: 10594

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.599 AC: 40702 AN: 67982

Other (OTH) AF: 0.448 AC: 947 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.1
DANN	Benign	0.66
PhyloP100		1.0
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

Other links and lift over

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