6-13634750-C-T

Position:

• chr6-13634750-C-T

Variant summary

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

The NM_005493.3(RANBP9):​c.1674-198G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,950 control chromosomes in the GnomAD database, including 14,567 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 0.43 (14567 hom., cov: 32)
• Consequence: RANBP9 NM_005493.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160

Genes affected

RANBP9 (HGNC:13727): (RAN binding protein 9) This gene encodes a protein that binds RAN, a small GTP binding protein belonging to the RAS superfamily that is essential for the translocation of RNA and proteins through the nuclear pore complex. The protein encoded by this gene has also been shown to interact with several other proteins, including met proto-oncogene, homeodomain interacting protein kinase 2, androgen receptor, and cyclin-dependent kinase 11. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RANBP9	NM_005493.3	c.1674-198G>A		intron_variant		ENST00000011619.6
RANBP9	XM_011514205.3	c.1526-2229G>A		intron_variant
RANBP9	XM_017010149.2	c.1008-198G>A		intron_variant
RANBP9	XM_047418032.1	c.987-198G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RANBP9	ENST00000011619.6	c.1674-198G>A		intron_variant		1	NM_005493.3	P1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65462 AN: 151832 Hom.: 14533 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.431 AC: 65553 AN: 151950 Hom.: 14567 Cov.: 32 AF XY: 0.434 AC XY: 32261 AN XY: 74262

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.403

Alfa AF: 0.392 Hom.: 17081

Bravo AF: 0.442

Asia WGS AF: 0.381 AC: 1327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.3
DANN	Benign	0.79

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: rs707816; hg19: chr6-13634982;