12-53991815-C-T

Variant names:

• chr12-53991815-C-T
• rs11614913
• ENST00000513209.1:c.166+5805C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000513209.1(ENSG00000273049):​c.166+5805C>T variant causes a intron 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: ENSG00000273049 ENST00000513209.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.65
• Publications: 686 publications found

Genes affected

ENSG00000273049 (HGNC:):

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MIR196A2	NR_029617.1	n.78C>T		non_coding_transcript_exon_variant	Exon 1 of 1
MIR196A2	unassigned_transcript_2005	n.17C>T		non_coding_transcript_exon_variant	Exon 1 of 1
MIR196A2	unassigned_transcript_2004	n.*32C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000273049	ENST00000513209.1	c.166+5805C>T		intron_variant	Intron 1 of 1	3		ENSP00000476742.1
MIR196A2	ENST00000385189.3	n.78C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
HOXC6	ENST00000504315.1	c.-193+1001C>T		intron_variant	Intron 1 of 1	3		ENSP00000424124.1

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

GnomAD2 exomes AF: 0.393 AC: 95196 AN: 242532 AF XY: 0.390

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 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

African (AFR) AF: 0.185 AC: 1926 AN: 10430

American (AMR) AF: 0.401 AC: 14318 AN: 35672

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 4627 AN: 11476

East Asian (EAS) AF: 0.546 AC: 7087 AN: 12976

South Asian (SAS) AF: 0.301 AC: 19668 AN: 65330

European-Finnish (FIN) AF: 0.440 AC: 14061 AN: 31976

Middle Eastern (MID) AF: 0.272 AC: 700 AN: 2578

European-Non Finnish (NFE) AF: 0.402 AC: 74622 AN: 185616

Other (OTH) AF: 0.391 AC: 6362 AN: 16262

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

African (AFR) AF: 0.186 AC: 7713 AN: 41470

American (AMR) AF: 0.385 AC: 5882 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1407 AN: 3472

East Asian (EAS) AF: 0.541 AC: 2786 AN: 5148

South Asian (SAS) AF: 0.289 AC: 1390 AN: 4810

European-Finnish (FIN) AF: 0.442 AC: 4664 AN: 10560

Middle Eastern (MID) AF: 0.281 AC: 82 AN: 292

European-Non Finnish (NFE) AF: 0.402 AC: 27337 AN: 67960

Other (OTH) AF: 0.365 AC: 768 AN: 2104

Alfa AF: 0.380 Hom.: 35053

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
PhyloP100		4.6

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: rs11614913; hg19: chr12-54385599;