rs11256802

Positions:

• chr10-6108538-A-C
• chr10-6108538-A-G

Variant summary

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

The NM_032905.5(RBM17):​c.506-148A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0912 in 555,128 control chromosomes in the GnomAD database, including 2,674 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 0.094 (745 hom., cov: 31)
  • Exomes 𝑓: 0.090 (1929 hom.)
• Consequence: RBM17 NM_032905.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.629

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM17	NM_032905.5	c.506-148A>C		intron_variant		ENST00000379888.9
RBM17	NM_001145547.2	c.506-148A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM17	ENST00000379888.9	c.506-148A>C		intron_variant		1	NM_032905.5	P1

Frequencies

GnomAD3 genomes AF: 0.0944 AC: 14336 AN: 151924 Hom.: 744 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0828

Gnomad ASJ AF: 0.0666

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.0910

Gnomad FIN AF: 0.0824

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0796

Gnomad OTH AF: 0.0953

GnomAD4 exome AF: 0.0900 AC: 36278 AN: 403086 Hom.: 1929 Cov.: 5 AF XY: 0.0895 AC XY: 19031 AN XY: 212592

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.0588

Gnomad4 ASJ exome AF: 0.0690

Gnomad4 EAS exome AF: 0.190

Gnomad4 SAS exome AF: 0.0871

Gnomad4 FIN exome AF: 0.0848

Gnomad4 NFE exome AF: 0.0806

Gnomad4 OTH exome AF: 0.0998

GnomAD4 genome AF: 0.0944 AC: 14354 AN: 152042 Hom.: 745 Cov.: 31 AF XY: 0.0953 AC XY: 7085 AN XY: 74332

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.0827

Gnomad4 ASJ AF: 0.0666

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.0915

Gnomad4 FIN AF: 0.0824

Gnomad4 NFE AF: 0.0796

Gnomad4 OTH AF: 0.0972

Alfa AF: 0.0765 Hom.: 491

Bravo AF: 0.0948

Asia WGS AF: 0.136 AC: 473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.5
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs11256802; hg19: chr10-6150501; COSMIC: COSV65914889; COSMIC: COSV65914889;