rs6060539

Positions:

• chr20-35651460-C-T

Variant summary

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

The NM_006047.6(RBM12):​c.*1064G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,096 control chromosomes in the GnomAD database, including 5,921 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 0.26 (5921 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: RBM12 NM_006047.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.692

Genes affected

RBM12 (HGNC:9898): (RNA binding motif protein 12) This gene encodes a protein that contains several RNA-binding motifs, potential transmembrane domains, and proline-rich regions. This gene and the gene for copine I overlap at map location 20q11.21. Alternative splicing in the 5' UTR results in four transcript variants. All variants encode the same protein. [provided by RefSeq, Nov 2010]

CPNE1 (HGNC:2314): (copine 1) Calcium-dependent membrane-binding proteins may regulate molecular events at the interface of the cell membrane and cytoplasm. This gene encodes a calcium-dependent protein that also contains two N-terminal type II C2 domains and an integrin A domain-like sequence in the C-terminus. However, the encoded protein does not contain a predicted signal sequence or transmembrane domains. This protein has a broad tissue distribution and it may function in membrane trafficking. This gene and the gene for RNA binding motif protein 12 overlap at map location 20q11.21. Alternate splicing results in multiple transcript variants encoding different proteins. [provided by RefSeq, Aug 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM12	NM_006047.6	c.*1064G>A		3_prime_UTR_variant	3/3	ENST00000374114.8	NP_006038.2
CPNE1	NM_152925.3	c.-1+13300G>A		intron_variant		ENST00000397443.7	NP_690902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM12	ENST00000374114.8	c.*1064G>A		3_prime_UTR_variant	3/3	1	NM_006047.6	ENSP00000363228	P1
CPNE1	ENST00000397443.7	c.-1+13300G>A		intron_variant		5	NM_152925.3	ENSP00000380585	P1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39286 AN: 151978 Hom.: 5876 Cov.: 32

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.248

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.259 AC: 39383 AN: 152096 Hom.: 5921 Cov.: 32 AF XY: 0.260 AC XY: 19306 AN XY: 74352

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.256

Alfa AF: 0.204 Hom.: 3316

Bravo AF: 0.259

Asia WGS AF: 0.342 AC: 1187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.3
DANN	Benign	0.85

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: rs6060539; hg19: chr20-34239382;