2-72728612-A-T

Position:

• chr2-72728612-A-T

Variant summary

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

The NM_015189.3(EXOC6B):​c.464+2395T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 152,092 control chromosomes in the GnomAD database, including 34,898 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 0.61 (34898 hom., cov: 31)
• Consequence: EXOC6B NM_015189.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61

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 (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOC6B	NM_015189.3	c.464+2395T>A		intron_variant		ENST00000272427.11	NP_056004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOC6B	ENST00000272427.11	c.464+2395T>A		intron_variant		1	NM_015189.3	ENSP00000272427.7
EXOC6B	ENST00000410104.1	c.464+2395T>A		intron_variant		1		ENSP00000386698.1
EXOC6B	ENST00000634650.1	c.464+2395T>A		intron_variant		5		ENSP00000489442.1
EXOC6B	ENST00000410112.6	n.*175+2395T>A		intron_variant		5		ENSP00000386634.2

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93332 AN: 151974 Hom.: 34904 Cov.: 31

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.902

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.658

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

GnomAD4 genome AF: 0.614 AC: 93330 AN: 152092 Hom.: 34898 Cov.: 31 AF XY: 0.626 AC XY: 46538 AN XY: 74334

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.810

Gnomad4 EAS AF: 0.990

Gnomad4 SAS AF: 0.903

Gnomad4 FIN AF: 0.811

Gnomad4 NFE AF: 0.767

Gnomad4 OTH AF: 0.657

Alfa AF: 0.673 Hom.: 4794

Bravo AF: 0.587

Asia WGS AF: 0.879 AC: 3055 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	5.9
DANN	Benign	0.73

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: rs1508061; hg19: chr2-72955741;