Genetic Variant ENSG00000273049:c.166+4593G>A (chr12-53990603-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000513209.1(ENSG00000273049):c.166+4593G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,176 control chromosomes in the GnomAD database, including 6,003 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 0.25 ( 6002 hom., cov: 31)

Exomes 𝑓: 0.13 ( 1 hom. )

Consequence

ENSG00000273049
ENST00000513209.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.378

Publications

4 publications found

Variant links:

Genes affected

ENSG00000273049 (HGNC:):

ENSG00000273049 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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000273049	ENST00000513209.1 link	c.166+4593G>A		intron_variant	Intron 1 of 1	3		ENSP00000476742.1		V9GYH0
HOXC6	ENST00000504315.1 link	c.-404G>A		upstream_gene_variant		3		ENSP00000424124.1		D6RBH4

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

37892

AN:

151974

Hom.:

5986

Cov.:

show subpopulations

Gnomad AFR

AF:

0.455

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.175

Gnomad ASJ

AF:

0.150

Gnomad EAS

AF:

0.224

Gnomad SAS

AF:

0.260

Gnomad FIN

AF:

0.0884

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.174

Gnomad OTH

AF:

0.248

GnomAD4 exome

AF:

0.131

AC:

AN:

Hom.:

Cov.:

AF XY:

0.155

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.172

AC:

AN:

Other (OTH)

AF:

0.125

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.249

AC:

37942

AN:

152092

Hom.:

6002

Cov.:

AF XY:

0.243

AC XY:

18089

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.455

AC:

18858

AN:

41438

American (AMR)

AF:

0.175

AC:

2676

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

521

AN:

3468

East Asian (EAS)

AF:

0.222

AC:

1152

AN:

5182

South Asian (SAS)

AF:

0.259

AC:

1247

AN:

4814

European-Finnish (FIN)

AF:

0.0884

AC:

937

AN:

10604

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.174

AC:

11844

AN:

67978

Other (OTH)

AF:

0.249

AC:

526

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1304

2608

3913

5217

6521

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

370

740

1110

1480

1850

<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:

0.204

Hom.:

4777

Bravo

AF:

0.262

Asia WGS

AF:

0.281

AC:

980

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

0.38

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over