rs2290225

chr7-128317549-A-Cchr7-128317549-A-Gchr7-128317549-A-T

Variant summary

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

The NM_018077.3(RBM28):c.1788+110T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 829,052 control chromosomes in the GnomAD database, including 114,535 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 0.46 (17418 hom., cov: 31)
  • Exomes 𝑓: 0.53 (97117 hom.)
• Consequence: RBM28 NM_018077.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM28	NM_018077.3	c.1788+110T>G		intron_variant		ENST00000223073.6
RBM28	NM_001166135.2	c.1365+110T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM28	ENST00000223073.6	c.1788+110T>G		intron_variant		1	NM_018077.3	P1
RBM28	ENST00000415472.6	c.1365+110T>G		intron_variant		2
RBM28	ENST00000481788.1	n.161-2529T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69903 AN: 151848 Hom.: 17414 Cov.: 31

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.456

GnomAD4 exome AF: 0.528 AC: 357538 AN: 677086 Hom.: 97117 AF XY: 0.528 AC XY: 191294 AN XY: 362322

Gnomad4 AFR exome AF: 0.267

Gnomad4 AMR exome AF: 0.619

Gnomad4 ASJ exome AF: 0.485

Gnomad4 EAS exome AF: 0.780

Gnomad4 SAS exome AF: 0.520

Gnomad4 FIN exome AF: 0.540

Gnomad4 NFE exome AF: 0.515

Gnomad4 OTH exome AF: 0.510

GnomAD4 genome AF: 0.460 AC: 69926 AN: 151966 Hom.: 17418 Cov.: 31 AF XY: 0.467 AC XY: 34704 AN XY: 74278

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.781

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.460

Alfa AF: 0.501 Hom.: 38619

Bravo AF: 0.452

Asia WGS AF: 0.616 AC: 2142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.7
Dann	Benign	0.62

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: rs2290225; hg19: chr7-127957602; COSMIC: COSV56161468; COSMIC: COSV56161468;