12-53999990-G-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000513209.1(ENSG00000273049):​c.166+13980G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 608,580 control chromosomes in the GnomAD database, including 94,755 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 0.55 ( 23257 hom., cov: 29)
Exomes 𝑓: 0.56 ( 71498 hom. )

Consequence

ENSG00000273049
ENST00000513209.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.50

Publications

9 publications found
Variant links:
Genes affected
HOXC-AS1 (HGNC:43749): (HOXC cluster antisense RNA 1)
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]
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HOXC-AS1NR_047504.1 linkn.21C>T non_coding_transcript_exon_variant Exon 1 of 2
HOXC9NM_006897.3 linkc.-199G>A upstream_gene_variant ENST00000303450.5 NP_008828.1 P31274A0A024RAZ6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ENSG00000273049ENST00000513209.1 linkc.166+13980G>A intron_variant Intron 1 of 1 3 ENSP00000476742.1 V9GYH0
HOXC9ENST00000303450.5 linkc.-199G>A upstream_gene_variant 1 NM_006897.3 ENSP00000302836.4 P31274

Frequencies

GnomAD3 genomes
AF:
0.553
AC:
83416
AN:
150858
Hom.:
23245
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.550
Gnomad AMI
AF:
0.520
Gnomad AMR
AF:
0.537
Gnomad ASJ
AF:
0.537
Gnomad EAS
AF:
0.763
Gnomad SAS
AF:
0.496
Gnomad FIN
AF:
0.492
Gnomad MID
AF:
0.519
Gnomad NFE
AF:
0.557
Gnomad OTH
AF:
0.574
GnomAD4 exome
AF:
0.556
AC:
254364
AN:
457604
Hom.:
71498
Cov.:
5
AF XY:
0.551
AC XY:
132535
AN XY:
240490
show subpopulations
African (AFR)
AF:
0.547
AC:
6571
AN:
12008
American (AMR)
AF:
0.516
AC:
8627
AN:
16728
Ashkenazi Jewish (ASJ)
AF:
0.543
AC:
7360
AN:
13556
East Asian (EAS)
AF:
0.722
AC:
21199
AN:
29362
South Asian (SAS)
AF:
0.499
AC:
21199
AN:
42442
European-Finnish (FIN)
AF:
0.515
AC:
15084
AN:
29312
Middle Eastern (MID)
AF:
0.558
AC:
1115
AN:
1998
European-Non Finnish (NFE)
AF:
0.554
AC:
158547
AN:
286194
Other (OTH)
AF:
0.564
AC:
14662
AN:
26004
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
5517
11035
16552
22070
27587
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
1084
2168
3252
4336
5420
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.553
AC:
83455
AN:
150976
Hom.:
23257
Cov.:
29
AF XY:
0.549
AC XY:
40484
AN XY:
73744
show subpopulations
African (AFR)
AF:
0.550
AC:
22557
AN:
41020
American (AMR)
AF:
0.536
AC:
8158
AN:
15210
Ashkenazi Jewish (ASJ)
AF:
0.537
AC:
1858
AN:
3462
East Asian (EAS)
AF:
0.762
AC:
3870
AN:
5076
South Asian (SAS)
AF:
0.495
AC:
2364
AN:
4778
European-Finnish (FIN)
AF:
0.492
AC:
5135
AN:
10438
Middle Eastern (MID)
AF:
0.524
AC:
154
AN:
294
European-Non Finnish (NFE)
AF:
0.557
AC:
37697
AN:
67696
Other (OTH)
AF:
0.568
AC:
1195
AN:
2104
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.498
Heterozygous variant carriers
0
1824
3647
5471
7294
9118
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
714
1428
2142
2856
3570
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.314
Hom.:
527
Asia WGS
AF:
0.582
AC:
2024
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
CADD
Benign
5.3
DANN
Benign
0.88
PhyloP100
-1.5
PromoterAI
0.047
Neutral
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs12817092; hg19: chr12-54393774; API