rs10279576

chr7-128325356-G-C

Variant summary

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

The NM_018077.3(RBM28):c.1203+462C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,148 control chromosomes in the GnomAD database, including 7,355 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 0.29 (7355 hom., cov: 33)
• Consequence: RBM28 NM_018077.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378

Genes affected

RBM28 (HGNC:21863): (RNA binding motif protein 28) The protein encoded by this gene is a specific nucleolar component of the spliceosomal small nuclear ribonucleoprotein (snRNP)complexes . It specifically associates with U1, U2, U4, U5, and U6 small nuclear RNAs (snRNAs), possibly coordinating their transition through the nucleolus. Mutation in this gene causes alopecia, progressive neurological defects, and endocrinopathy (ANE syndrome), a pleiotropic and clinically heterogeneous disorder. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

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 (EAS) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM28	NM_018077.3	c.1203+462C>G		intron_variant		ENST00000223073.6
RBM28	NM_001166135.2	c.780+462C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM28	ENST00000223073.6	c.1203+462C>G		intron_variant		1	NM_018077.3	P1
RBM28	ENST00000415472.6	c.780+462C>G		intron_variant		2
RBM28	ENST00000487602.5	c.547-662C>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44666 AN: 152030 Hom.: 7347 Cov.: 33

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.294 AC: 44696 AN: 152148 Hom.: 7355 Cov.: 33 AF XY: 0.298 AC XY: 22153 AN XY: 74354

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.309

Alfa AF: 0.291 Hom.: 832

Bravo AF: 0.304

Asia WGS AF: 0.460 AC: 1601 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	0.55
Dann	Benign	0.57

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: rs10279576; hg19: chr7-127965409;