dbSNP rs3809783: HOXB3:c.-424-5802T>C (chr17-48579816-A-G) – 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 NM_001384749.1(HOXB3):c.-424-5802T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000327 in 305,656 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)

Exomes 𝑓: 0.0000033 ( 0 hom. )

Consequence

HOXB3
NM_001384749.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0610

Publications

0 publications found

Variant links:

Genes affected

HOXB3 (HGNC:5114): (homeobox B3) This gene is a member of the Antp homeobox family and encodes a nuclear protein with a homeobox DNA-binding domain. It is included in a cluster of homeobox B genes located on chromosome 17. The encoded protein functions as a sequence-specific transcription factor that is involved in development. Increased expression of this gene is associated with a distinct biologic subset of acute myeloid leukemia (AML). [provided by RefSeq, Jul 2008]

HOXB3 links:

ENSG00000257178 (HGNC:):

ENSG00000257178 links:

HOXB-AS3 (HGNC:40283): (HOXB cluster antisense RNA 3)

HOXB-AS3 links:

MIR10A (HGNC:31497): (microRNA 10a) 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]

MIR10A 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=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384749.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HOXB3	NM_001384749.1	MANE Select	c.-424-5802T>C	intron	N/A	NP_001371678.1	P14651-1
HOXB3	NM_001384747.1		c.-14+10309T>C	intron	N/A	NP_001371676.1	P14651-1
HOXB3	NM_001330322.2		c.-372+2476T>C	intron	N/A	NP_001317251.1	P14651-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HOXB3	ENST00000498678.6	TSL:2 MANE Select	c.-424-5802T>C	intron	N/A	ENSP00000420595.1	P14651-1
HOXB3	ENST00000476342.1	TSL:1	c.-14+10309T>C	intron	N/A	ENSP00000418892.1	P14651-1
HOXB3	ENST00000866120.1		c.-518-5802T>C	intron	N/A	ENSP00000536179.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000327

AC:

AN:

305656

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

175788

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

5810

American (AMR)

AF:

0.00

AC:

AN:

22916

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9710

East Asian (EAS)

AF:

0.00

AC:

AN:

9344

South Asian (SAS)

AF:

0.0000183

AC:

AN:

54524

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29152

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1624

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

159436

Other (OTH)

AF:

0.00

AC:

AN:

13140

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.1

(source)

DANN

Benign

0.47

PhyloP100

0.061

PromoterAI

-0.041

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over