rs10680577

Variant names:

• chr19-40798690-A-ATTAC
• rs10680577
• ENST00000594136.2:n.*16-1649_*16-1648insTTAC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000594136.2(RAB4B-EGLN2):​n.*16-1649_*16-1648insTTAC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.80 (48383 hom., cov: 0)
• Consequence: RAB4B-EGLN2 ENST00000594136.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.811
• Publications: 17 publications found

Genes affected

RAB4B-EGLN2 (HGNC:44465): (RAB4B-EGLN2 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring RAB4B (RAB4B, member RAS oncogene family) and EGLN2 (egl nine homolog 2) genes on chromosome 19. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ENSG00000306007 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB4B-EGLN2	NR_037791.1	n.815-1647_815-1644dupTACT		intron_variant	Intron 7 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB4B-EGLN2	ENST00000594136.2	n.*16-1649_*16-1648insTTAC		intron_variant	Intron 7 of 11	2		ENSP00000469872.1
RAB4B-EGLN2	ENST00000596216.2	n.875-1649_875-1648insTTAC		intron_variant	Intron 5 of 5	3
RAB4B-EGLN2	ENST00000601949.5	n.378-1649_378-1648insTTAC		intron_variant	Intron 3 of 3	4
ENSG00000306007	ENST00000814696.1	n.50+24_50+25insGTAA		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.797 AC: 120784 AN: 151566 Hom.: 48325 Cov.: 0

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.778

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.846

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.778

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

GnomAD4 genome AF: 0.797 AC: 120906 AN: 151686 Hom.: 48383 Cov.: 0 AF XY: 0.796 AC XY: 59014 AN XY: 74092

African (AFR) AF: 0.839 AC: 34726 AN: 41368

American (AMR) AF: 0.809 AC: 12343 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.787 AC: 2732 AN: 3470

East Asian (EAS) AF: 0.728 AC: 3743 AN: 5138

South Asian (SAS) AF: 0.649 AC: 3125 AN: 4818

European-Finnish (FIN) AF: 0.846 AC: 8896 AN: 10514

Middle Eastern (MID) AF: 0.753 AC: 220 AN: 292

European-Non Finnish (NFE) AF: 0.778 AC: 52788 AN: 67828

Other (OTH) AF: 0.777 AC: 1634 AN: 2104

Alfa AF: 0.779 Hom.: 4922

Asia WGS AF: 0.720 AC: 2503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.81

Splicing

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

Other links and lift over

dbSNP: rs10680577; hg19: chr19-41304595;