rs2308135

Variant names:

• chr11-66628514-C-CTAA
• rs2308135
• NM_006328.4:c.*1847_*1849dupTAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_006328.4(RBM14):​c.*1847_*1849dupTAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (15854 hom., cov: 0)
• Consequence: RBM14 NM_006328.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257
• Publications: 5 publications found

Genes affected

RBM14 (HGNC:14219): (RNA binding motif protein 14) This gene encodes a ribonucleoprotein that functions as a general nuclear coactivator, and an RNA splicing modulator. This protein contains two RNA recognition motifs (RRM) at the N-terminus, and multiple hexapeptide repeat domain at the C-terminus that interacts with thyroid hormone receptor-binding protein (TRBP), and is required for transcription activation. Alternatively spliced transcript variants encoding different isoforms (with opposing effects on transcription) have been described for this gene. [provided by RefSeq, Oct 2011]

RBM14-RBM4 (HGNC:38840): (RBM14-RBM4 readthrough) This locus represents naturally occurring read-through transcription between the neighboring RBM14 (RNA binding motif protein 14) and RBM4 (RNA binding motif protein 4) genes. Alternative splicing results in multiple transcript variants, one of which encodes a fusion protein that shares sequence identity with each individual gene product. This fusion protein contains RRM and zinc finger domains, and it functions to stimulate transcription in a hormone and receptor-dependent manner. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM14	NM_006328.4	c.*1847_*1849dupTAA		3_prime_UTR_variant	Exon 3 of 3	ENST00000310137.5	NP_006319.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM14	ENST00000310137.5	c.*1847_*1849dupTAA		3_prime_UTR_variant	Exon 3 of 3	1	NM_006328.4	ENSP00000311747.5
RBM14-RBM4	ENST00000412278.2	c.337+11458_337+11460dupTAA		intron_variant	Intron 1 of 2	2		ENSP00000388552.2

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65226 AN: 151620 Hom.: 15847 Cov.: 0

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.430 AC: 65231 AN: 151738 Hom.: 15854 Cov.: 0 AF XY: 0.434 AC XY: 32183 AN XY: 74152

African (AFR) AF: 0.181 AC: 7513 AN: 41406

American (AMR) AF: 0.594 AC: 9038 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1723 AN: 3466

East Asian (EAS) AF: 0.456 AC: 2353 AN: 5164

South Asian (SAS) AF: 0.600 AC: 2887 AN: 4814

European-Finnish (FIN) AF: 0.442 AC: 4649 AN: 10516

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35370 AN: 67846

Other (OTH) AF: 0.466 AC: 981 AN: 2106

Alfa AF: 0.454 Hom.: 2015

Bravo AF: 0.429

Asia WGS AF: 0.494 AC: 1716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2308135; hg19: chr11-66395985; COSMIC: COSV59557519; COSMIC: COSV59557519;