21-14227444-T-C

Variant names:

• chr21-14227444-T-C
• rs2822445
• NM_144770.5:c.*151T>C

Variant summary

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

The NM_144770.5(RBM11):​c.*151T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 858,740 control chromosomes in the GnomAD database, including 76,533 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 0.43 (13838 hom., cov: 32)
  • Exomes 𝑓: 0.42 (62695 hom.)
• Consequence: RBM11 NM_144770.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.825

Genes affected

RBM11 (HGNC:9897): (RNA binding motif protein 11) Enables poly(U) RNA binding activity and protein homodimerization activity. Acts upstream of or within cellular response to oxidative stress and regulation of alternative mRNA splicing, via spliceosome. Located in nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM11	NM_144770.5	c.*151T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000400577.4	NP_658983.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM11	ENST00000400577.4	c.*151T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_144770.5	ENSP00000383421.3
RBM11	ENST00000468643.5	n.1064T>C		non_coding_transcript_exon_variant	Exon 5 of 5	1
RBM11	ENST00000495055.1	n.868T>C		non_coding_transcript_exon_variant	Exon 4 of 4	1
RBM11	ENST00000475864.1	n.*60T>C		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64577 AN: 151858 Hom.: 13829 Cov.: 32

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.474

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.427

GnomAD4 exome AF: 0.422 AC: 298005 AN: 706764 Hom.: 62695 Cov.: 9 AF XY: 0.424 AC XY: 150391 AN XY: 354400

Gnomad4 AFR exome AF: 0.432

Gnomad4 AMR exome AF: 0.426

Gnomad4 ASJ exome AF: 0.440

Gnomad4 EAS exome AF: 0.510

Gnomad4 SAS exome AF: 0.498

Gnomad4 FIN exome AF: 0.403

Gnomad4 NFE exome AF: 0.410

Gnomad4 OTH exome AF: 0.428

GnomAD4 genome AF: 0.425 AC: 64620 AN: 151976 Hom.: 13838 Cov.: 32 AF XY: 0.425 AC XY: 31567 AN XY: 74290

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.460

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.424

Alfa AF: 0.419 Hom.: 9972

Bravo AF: 0.428

Asia WGS AF: 0.484 AC: 1680 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Benign	0.89

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: rs2822445; hg19: chr21-15599765;