rs274793

Variant names:

• chr19-5928174-T-C
• rs274793
• NM_007322.3:c.694-87A>G

Variant summary

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

The NM_007322.3(RANBP3):​c.694-87A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 1,483,708 control chromosomes in the GnomAD database, including 356,156 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 0.68 (35381 hom., cov: 31)
  • Exomes 𝑓: 0.69 (320775 hom.)
• Consequence: RANBP3 NM_007322.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.682
• Publications: 18 publications found

Genes affected

RANBP3 (HGNC:9850): (RAN binding protein 3) This gene encodes a protein with a RanBD1 domain that is found in both the nucleus and cytoplasm. This protein plays a role in nuclear export as part of a heteromeric complex. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RANBP3	NM_007322.3	c.694-87A>G		intron_variant	Intron 8 of 16	ENST00000340578.10	NP_015561.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RANBP3	ENST00000340578.10	c.694-87A>G		intron_variant	Intron 8 of 16	1	NM_007322.3	ENSP00000341483.5

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103396 AN: 151834 Hom.: 35350 Cov.: 31

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.781

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.682

GnomAD4 exome AF: 0.693 AC: 922376 AN: 1331756 Hom.: 320775 Cov.: 18 AF XY: 0.693 AC XY: 456690 AN XY: 659200

African (AFR) AF: 0.682 AC: 20364 AN: 29856

American (AMR) AF: 0.836 AC: 28371 AN: 33928

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 14387 AN: 20962

East Asian (EAS) AF: 0.736 AC: 28183 AN: 38272

South Asian (SAS) AF: 0.738 AC: 52931 AN: 71690

European-Finnish (FIN) AF: 0.555 AC: 22342 AN: 40288

Middle Eastern (MID) AF: 0.722 AC: 3204 AN: 4436

European-Non Finnish (NFE) AF: 0.689 AC: 714202 AN: 1036914

Other (OTH) AF: 0.693 AC: 38392 AN: 55410

GnomAD4 genome AF: 0.681 AC: 103481 AN: 151952 Hom.: 35381 Cov.: 31 AF XY: 0.680 AC XY: 50528 AN XY: 74268

African (AFR) AF: 0.673 AC: 27868 AN: 41426

American (AMR) AF: 0.781 AC: 11926 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2401 AN: 3470

East Asian (EAS) AF: 0.734 AC: 3780 AN: 5150

South Asian (SAS) AF: 0.748 AC: 3594 AN: 4808

European-Finnish (FIN) AF: 0.535 AC: 5657 AN: 10564

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.678 AC: 46082 AN: 67950

Other (OTH) AF: 0.682 AC: 1440 AN: 2110

Alfa AF: 0.683 Hom.: 7606

Bravo AF: 0.697

Asia WGS AF: 0.720 AC: 2501 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.18
DANN	Benign	0.45
PhyloP100		-0.68
Mutation Taster		=12/88	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: 5

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

Other links and lift over

dbSNP: rs274793; hg19: chr19-5928185; COSMIC: COSV50380784; COSMIC: COSV50380784;