rs4747880

Positions:

• chr10-6111004-C-T

Variant summary

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

The NM_032905.5(RBM17):​c.704+877C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,022 control chromosomes in the GnomAD database, including 10,625 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 0.36 (10625 hom., cov: 33)
• Consequence: RBM17 NM_032905.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.592

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM17	NM_032905.5	c.704+877C>T		intron_variant		ENST00000379888.9	NP_116294.1
RBM17	NM_001145547.2	c.704+877C>T		intron_variant			NP_001139019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM17	ENST00000379888.9	c.704+877C>T		intron_variant		1	NM_032905.5	ENSP00000369218	P1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55365 AN: 151904 Hom.: 10610 Cov.: 33

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.365 AC: 55415 AN: 152022 Hom.: 10625 Cov.: 33 AF XY: 0.371 AC XY: 27584 AN XY: 74296

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.389

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.393

Alfa AF: 0.362 Hom.: 1275

Bravo AF: 0.372

Asia WGS AF: 0.447 AC: 1557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.0
DANN	Benign	0.53

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: rs4747880; hg19: chr10-6152967;