chr16-2141733-A-G

Position:

• chr16-2141733-A-G

Variant summary

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

The ENST00000565592.5(RAB26):​c.-4+784A>G variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 151,914 control chromosomes in the GnomAD database, including 43,561 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 0.74 (43561 hom., cov: 30)
• Consequence: RAB26 ENST00000565592.5 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800

Genes affected

RAB26 (HGNC:14259): (RAB26, member RAS oncogene family) Members of the RAB protein family, including RAB26, are important regulators of vesicular fusion and trafficking. The RAB family of small G proteins regulates intercellular vesicle trafficking, including exocytosis, endocytosis, and recycling (summary by Seki et al., 2000 [PubMed 11043516]).[supplied by OMIM, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB26	ENST00000565592.5	c.-4+784A>G		intron_variant, NMD_transcript_variant		1		ENSP00000454373

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112742 AN: 151796 Hom.: 43543 Cov.: 30

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.739

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

GnomAD4 genome AF: 0.742 AC: 112790 AN: 151914 Hom.: 43561 Cov.: 30 AF XY: 0.747 AC XY: 55452 AN XY: 74250

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.789

Gnomad4 ASJ AF: 0.746

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.925

Gnomad4 FIN AF: 0.825

Gnomad4 NFE AF: 0.820

Gnomad4 OTH AF: 0.742

Alfa AF: 0.795 Hom.: 34659

Bravo AF: 0.730

Asia WGS AF: 0.923 AC: 3209 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.6
DANN	Benign	0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs258281; hg19: chr16-2191734;