12-53991815-C-T

Position:

• chr12-53991815-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NR_029617.1(MIR196A2):​n.78C>T variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.373 in 524,320 control chromosomes in the GnomAD database, including 38,322 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 0.34 (9923 hom., cov: 32)
  • Exomes 𝑓: 0.39 (28399 hom.)
• Consequence: MIR196A2 NR_029617.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.65

Genes affected

MIR196A2 (HGNC:31568): (microRNA 196a-2) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

HOXC6 (HGNC:5128): (homeobox C6) This gene belongs to the homeobox family, members of which encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, which are located on different chromosomes and consist of 9 to 11 genes arranged in tandem. This gene, HOXC6, is one of several HOXC genes located in a cluster on chromosome 12. Three genes, HOXC5, HOXC4 and HOXC6, share a 5' non-coding exon. Transcripts may include the shared exon spliced to the gene-specific exons, or they may include only the gene-specific exons. Alternatively spliced transcript variants encoding different isoforms have been identified for HOXC6. Transcript variant two includes the shared exon, and transcript variant one includes only gene-specific exons. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIR196A2	NR_029617.1	n.78C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIR196A2	ENST00000385189.3	n.78C>T		mature_miRNA_variant	1/1
HOXC6	ENST00000504315.1	c.-193+1001C>T		intron_variant		3		ENSP00000424124

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52412 AN: 151886 Hom.: 9919 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.368

GnomAD3 exomes AF: 0.393 AC: 95196 AN: 242532 Hom.: 19177 AF XY: 0.390 AC XY: 51148 AN XY: 131056

Gnomad AFR exome AF: 0.186

Gnomad AMR exome AF: 0.403

Gnomad ASJ exome AF: 0.403

Gnomad EAS exome AF: 0.552

Gnomad SAS exome AF: 0.299

Gnomad FIN exome AF: 0.446

Gnomad NFE exome AF: 0.406

Gnomad OTH exome AF: 0.385

GnomAD4 exome AF: 0.385 AC: 143371 AN: 372316 Hom.: 28399 Cov.: 0 AF XY: 0.378 AC XY: 79947 AN XY: 211382

Gnomad4 AFR exome AF: 0.185

Gnomad4 AMR exome AF: 0.401

Gnomad4 ASJ exome AF: 0.403

Gnomad4 EAS exome AF: 0.546

Gnomad4 SAS exome AF: 0.301

Gnomad4 FIN exome AF: 0.440

Gnomad4 NFE exome AF: 0.402

Gnomad4 OTH exome AF: 0.391

GnomAD4 genome AF: 0.345 AC: 52425 AN: 152004 Hom.: 9923 Cov.: 32 AF XY: 0.347 AC XY: 25757 AN XY: 74280

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.541

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.365

Alfa AF: 0.377 Hom.: 17871

Bravo AF: 0.339

Asia WGS AF: 0.346 AC: 1206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Benign	0.91

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: rs11614913; hg19: chr12-54385599;