NM_018077.3:c.*125C>G

Variant names:

• chr7-128310672-G-C
• rs12850
• NM_018077.3:c.*125C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018077.3(RBM28):​c.*125C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000866 in 1,154,942 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
• Consequence: RBM28 NM_018077.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.625
• Publications: 15 publications found

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]

RBM28 Gene-Disease associations (from GenCC):

• ANE syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM28	NM_018077.3	c.*125C>G		3_prime_UTR_variant	Exon 19 of 19	ENST00000223073.6	NP_060547.2
RBM28	NM_001166135.2	c.*125C>G		3_prime_UTR_variant	Exon 15 of 15		NP_001159607.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM28	ENST00000223073.6	c.*125C>G		3_prime_UTR_variant	Exon 19 of 19	1	NM_018077.3	ENSP00000223073.1
RBM28	ENST00000481788.1	n.777C>G		non_coding_transcript_exon_variant	Exon 4 of 4	3
RBM28	ENST00000415472.6	c.*125C>G		3_prime_UTR_variant	Exon 15 of 15	2		ENSP00000390517.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.66e-7 AC: 1 AN: 1154942 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 588912

African (AFR) AF: 0.00 AC: 0 AN: 27342

American (AMR) AF: 0.0000227 AC: 1 AN: 44126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24158

East Asian (EAS) AF: 0.00 AC: 0 AN: 38328

South Asian (SAS) AF: 0.00 AC: 0 AN: 79440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5192

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 845480

Other (OTH) AF: 0.00 AC: 0 AN: 50706

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.59
PhyloP100		-0.63
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

Other links and lift over

dbSNP: rs12850; hg19: chr7-127950725;