rs2274359

Positions:

• chr10-6113843-T-C

Variant summary

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

The NM_032905.5(RBM17):​c.931-206T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 586,974 control chromosomes in the GnomAD database, including 23,412 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 0.22 (4735 hom., cov: 33)
  • Exomes 𝑓: 0.28 (18677 hom.)
• Consequence: RBM17 NM_032905.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.834

Genes affected

RBM17 (HGNC:16944): (RNA binding motif protein 17) This gene encodes an RNA binding protein. The encoded protein is part of the spliceosome complex and functions in the second catalytic step of mRNA splicing. Alternatively spliced transcript variants have been described. Related pseudogenes exist on chromosomes 9 and 15. [provided by RefSeq, Mar 2009]

RBM17 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM17	NM_032905.5	c.931-206T>C		intron_variant		ENST00000379888.9	NP_116294.1
RBM17	NM_001145547.2	c.931-206T>C		intron_variant			NP_001139019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM17	ENST00000379888.9	c.931-206T>C		intron_variant		1	NM_032905.5	ENSP00000369218.4
RBM17	ENST00000446108.5	c.931-206T>C		intron_variant		1		ENSP00000388638.1
RBM17	ENST00000465906.5	n.220-206T>C		intron_variant		2
RBM17	ENST00000476706.5	n.442-206T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33851 AN: 152156 Hom.: 4734 Cov.: 33

Gnomad AFR AF: 0.0598

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.275

GnomAD4 exome AF: 0.284 AC: 123325 AN: 434700 Hom.: 18677 AF XY: 0.287 AC XY: 65755 AN XY: 229048

Gnomad4 AFR exome AF: 0.0625

Gnomad4 AMR exome AF: 0.285

Gnomad4 ASJ exome AF: 0.448

Gnomad4 EAS exome AF: 0.159

Gnomad4 SAS exome AF: 0.302

Gnomad4 FIN exome AF: 0.239

Gnomad4 NFE exome AF: 0.302

Gnomad4 OTH exome AF: 0.282

GnomAD4 genome AF: 0.222 AC: 33850 AN: 152274 Hom.: 4735 Cov.: 33 AF XY: 0.220 AC XY: 16414 AN XY: 74458

Gnomad4 AFR AF: 0.0597

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.275

Alfa AF: 0.261 Hom.: 1173

Bravo AF: 0.217

Asia WGS AF: 0.231 AC: 805 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	1.1
DANN	Benign	0.49

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: rs2274359; hg19: chr10-6155806;