dbSNP rs4759315: HOXC11:p.Ser12Ser (chr12-53973277-T-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_014212.4(HOXC11):c.36T>G(p.Ser12Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 1,612,844 control chromosomes in the GnomAD database, including 806,272 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 1.0 ( 76054 hom., cov: 31)

Exomes 𝑓: 1.0 ( 730218 hom. )

Consequence

HOXC11
NM_014212.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.872

Publications

12 publications found

Variant links:

Genes affected

HOXC11 (HGNC:5123): (homeobox C11) 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. The product of this gene binds to a promoter element of the lactase-phlorizin hydrolase. It also may play a role in early intestinal development. An alternatively spliced variant encoding a shorter isoform has been described but its full-length nature has not been determined. [provided by RefSeq, Jul 2008]

HOXC11 links:

HOTAIR (HGNC:33510): (HOX transcript antisense RNA) This gene is located within the Homeobox C (HOXC) gene cluster on chromosome 12 and is co-expressed with the HOXC genes. It functions through an RNA product, which binds lysine specific demethylase 1 (LSD1) and Polycomb repressive complex 2 (PRC2), and serves as a scaffold to assemble these regulators at the HOXD gene cluster, thereby promoting epigenetic repression of HOXD. This gene is highly expressed in multiple tumors. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Feb 2019]

HOTAIR links:

ENSG00000293681 (HGNC:):

ENSG00000293681 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP7

Synonymous conserved (PhyloP=0.872 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXC11	NM_014212.4 link	c.36T>G	p.Ser12Ser	synonymous_variant	Exon 1 of 2	ENST00000546378.1	NP_055027.1	O43248

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXC11	ENST00000546378.1 link	c.36T>G	p.Ser12Ser	synonymous_variant	Exon 1 of 2	1	NM_014212.4	ENSP00000446680.1		O43248

Frequencies

GnomAD3 genomes

AF:

0.999

AC:

152070

AN:

152148

Hom.:

75996

Cov.:

show subpopulations

Gnomad AFR

AF:

0.998

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

1.00

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

1.00

GnomAD2 exomes

AF:

1.00

AC:

249845

AN:

249880

AF XY:

1.00

show subpopulations

Gnomad AFR exome

AF:

0.998

Gnomad AMR exome

AF:

1.00

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

AF:

1.00

AC:

1460507

AN:

1460578

Hom.:

730218

Cov.:

AF XY:

1.00

AC XY:

726644

AN XY:

726678

show subpopulations

African (AFR)

AF:

0.998

AC:

33427

AN:

33478

American (AMR)

AF:

1.00

AC:

44698

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

26092

AN:

26092

East Asian (EAS)

AF:

1.00

AC:

39695

AN:

39696

South Asian (SAS)

AF:

1.00

AC:

86216

AN:

86216

European-Finnish (FIN)

AF:

1.00

AC:

52515

AN:

52516

Middle Eastern (MID)

AF:

1.00

AC:

5762

AN:

5762

European-Non Finnish (NFE)

AF:

1.00

AC:

1111746

AN:

1111748

Other (OTH)

AF:

1.00

AC:

60356

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

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

21670

43340

65010

86680

108350

<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:

0.999

AC:

152187

AN:

152266

Hom.:

76054

Cov.:

AF XY:

1.00

AC XY:

74411

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.998

AC:

41473

AN:

41552

American (AMR)

AF:

1.00

AC:

15312

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5134

AN:

5134

South Asian (SAS)

AF:

1.00

AC:

4814

AN:

4814

European-Finnish (FIN)

AF:

1.00

AC:

10630

AN:

10630

Middle Eastern (MID)

AF:

1.00

AC:

294

AN:

294

European-Non Finnish (NFE)

AF:

1.00

AC:

68030

AN:

68030

Other (OTH)

AF:

1.00

AC:

2116

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

916

1832

2748

3664

4580

<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:

1.00

Hom.:

14360

Bravo

AF:

0.999

Asia WGS

AF:

1.00

AC:

3478

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

0.87

PromoterAI

-0.029

Neutral

(source)

Mutation Taster

=91/9

polymorphism (auto)

(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