NM_015189.3:c.847-2667T>C

Variant names:

• chr2-72562188-A-G
• rs12471136
• NM_015189.3:c.847-2667T>C

Variant summary

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

The NM_015189.3(EXOC6B):​c.847-2667T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 152,084 control chromosomes in the GnomAD database, including 58,118 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 0.87 (58118 hom., cov: 31)
• Consequence: EXOC6B NM_015189.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.77
• Publications: 2 publications found

Genes affected

EXOC6B (HGNC:17085): (exocyst complex component 6B) This gene encodes a protein which is a part of the evolutionarily conserved exocyst, a multimeric protein complex necessary for exocytosis, which in turn, is crucial for cell growth, polarity and migration. Disruption of this gene may be associated with phenotypes exhibiting multiple symptoms including intellectual disability and developmental delay (DD). [provided by RefSeq, Jun 2016]

EXOC6B Gene-Disease associations (from GenCC):

• spondyloepimetaphyseal dysplasia with joint laxity, type 3

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• spondyloepimetaphyseal dysplasia with joint laxity

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015189.3. 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
	EXOC6B	NM_015189.3	MANE Select	c.847-2667T>C		intron	N/A	NP_056004.1
	EXOC6B	NM_001321729.2		c.847-2667T>C		intron	N/A	NP_001308658.1
	EXOC6B	NM_001321731.2		c.847-2667T>C		intron	N/A	NP_001308660.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC6B	ENST00000272427.11	TSL:1 MANE Select	c.847-2667T>C		intron	N/A	ENSP00000272427.7
	EXOC6B	ENST00000410104.1	TSL:1	c.847-2667T>C		intron	N/A	ENSP00000386698.1
	EXOC6B	ENST00000634650.1	TSL:5	c.847-2667T>C		intron	N/A	ENSP00000489442.1

Frequencies

GnomAD3 genomes AF: 0.873 AC: 132670 AN: 151966 Hom.: 58090 Cov.: 31

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.921

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.894

Gnomad OTH AF: 0.871

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

GnomAD4 genome AF: 0.873 AC: 132747 AN: 152084 Hom.: 58118 Cov.: 31 AF XY: 0.877 AC XY: 65171 AN XY: 74352

African (AFR) AF: 0.791 AC: 32851 AN: 41512

American (AMR) AF: 0.904 AC: 13795 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.906 AC: 3141 AN: 3468

East Asian (EAS) AF: 0.994 AC: 5137 AN: 5168

South Asian (SAS) AF: 0.933 AC: 4493 AN: 4818

European-Finnish (FIN) AF: 0.921 AC: 9753 AN: 10592

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.894 AC: 60733 AN: 67948

Other (OTH) AF: 0.866 AC: 1833 AN: 2116

Alfa AF: 0.884 Hom.: 23680

Bravo AF: 0.867

Asia WGS AF: 0.945 AC: 3287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.86
PhyloP100		2.8
Mutation Taster		=99/1	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: rs12471136; hg19: chr2-72789317;