rs41417

Positions:

• chr2-72176719-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015189.3(EXOC6B):​c.*2616A>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 0.14 in 152,198 control chromosomes in the GnomAD database, including 1,900 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 0.14 (1899 hom., cov: 32)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: EXOC6B NM_015189.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOC6B	NM_015189.3	c.*2616A>G		3_prime_UTR_variant	22/22	ENST00000272427.11	NP_056004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOC6B	ENST00000272427	c.*2616A>G		3_prime_UTR_variant	22/22	1	NM_015189.3	ENSP00000272427.7

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21237 AN: 152076 Hom.: 1898 Cov.: 32

Gnomad AFR AF: 0.0504

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.0995

Gnomad EAS AF: 0.0243

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.140

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.140 AC: 21239 AN: 152194 Hom.: 1899 Cov.: 32 AF XY: 0.139 AC XY: 10372 AN XY: 74398

Gnomad4 AFR AF: 0.0503

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.0995

Gnomad4 EAS AF: 0.0244

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.143

Alfa AF: 0.157 Hom.: 563

Bravo AF: 0.133

Asia WGS AF: 0.0680 AC: 234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.64

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: rs41417; hg19: chr2-72403848;