rs2290225

Variant names:

• chr7-128317549-A-C
• rs2290225
• NM_018077.3:c.1788+110T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-128317549-A-C
• chr7-128317549-A-G
• chr7-128317549-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
RBM28	NM_018077.3	c.1788+110T>G		intron_variant	Intron 16 of 18	ENST00000223073.6	NP_060547.2
RBM28	NM_001166135.2	c.1365+110T>G		intron_variant	Intron 12 of 14		NP_001159607.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM28	ENST00000223073.6	c.1788+110T>G		intron_variant	Intron 16 of 18	1	NM_018077.3	ENSP00000223073.1
RBM28	ENST00000415472.6	c.1365+110T>G		intron_variant	Intron 12 of 14	2		ENSP00000390517.2
RBM28	ENST00000481788.1	n.161-2529T>G		intron_variant	Intron 1 of 3	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

African (AFR) AF: 0.267 AC: 4835 AN: 18092

American (AMR) AF: 0.619 AC: 22762 AN: 36794

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 9951 AN: 20536

East Asian (EAS) AF: 0.780 AC: 27206 AN: 34900

South Asian (SAS) AF: 0.520 AC: 34332 AN: 66058

European-Finnish (FIN) AF: 0.540 AC: 21832 AN: 40434

Middle Eastern (MID) AF: 0.445 AC: 1280 AN: 2874

European-Non Finnish (NFE) AF: 0.515 AC: 217913 AN: 423204

Other (OTH) AF: 0.510 AC: 17427 AN: 34194

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

African (AFR) AF: 0.269 AC: 11154 AN: 41472

American (AMR) AF: 0.550 AC: 8395 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1653 AN: 3468

East Asian (EAS) AF: 0.781 AC: 4037 AN: 5166

South Asian (SAS) AF: 0.521 AC: 2507 AN: 4816

European-Finnish (FIN) AF: 0.549 AC: 5783 AN: 10538

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.511 AC: 34746 AN: 67938

Other (OTH) AF: 0.460 AC: 968 AN: 2106

Alfa AF: 0.491 Hom.: 62734

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
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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