Genetic Variant ENSG00000273049:c.166+13980G>C (chr12-53999990-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000513209.1(ENSG00000273049):c.166+13980G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 29)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ENSG00000273049
ENST00000513209.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.50

Publications

9 publications found

Variant links:

Genes affected

ENSG00000273049 (HGNC:):

ENSG00000273049 links:

HOXC-AS1 (HGNC:43749): (HOXC cluster antisense RNA 1)

HOXC-AS1 links:

HOXC9 (HGNC:5130): (homeobox C9) This gene belongs to the homeobox family of genes. The homeobox genes 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 is one of several homeobox HOXC genes located in a cluster on chromosome 12. [provided by RefSeq, Jul 2008]

HOXC9 links:

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]

HOXC6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXC-AS1	NR_047504.1 link	n.21C>G		non_coding_transcript_exon_variant	Exon 1 of 2
HOXC9	NM_006897.3 link	c.-199G>C		upstream_gene_variant		ENST00000303450.5	NP_008828.1	P31274A0A024RAZ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000273049	ENST00000513209.1 link	c.166+13980G>C		intron_variant	Intron 1 of 1	3		ENSP00000476742.1		V9GYH0
HOXC9	ENST00000303450.5 link	c.-199G>C		upstream_gene_variant		1	NM_006897.3	ENSP00000302836.4		P31274

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

458270

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

240846

African (AFR)

AF:

0.00

AC:

AN:

12042

American (AMR)

AF:

0.00

AC:

AN:

16758

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13580

East Asian (EAS)

AF:

0.00

AC:

AN:

29400

South Asian (SAS)

AF:

0.00

AC:

AN:

42508

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29340

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2000

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

286614

Other (OTH)

AF:

0.00

AC:

AN:

26028

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

527

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

4.2

(source)

DANN

Benign

0.64

PhyloP100

-1.5

PromoterAI

0.018

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over