rs3809783

Variant names:

• chr17-48579816-A-G
• rs3809783
• NM_001384749.1:c.-424-5802T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-48579816-A-G
• chr17-48579816-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 0 publications found

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]

ENSG00000257178 (HGNC:):

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

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]

ACMG classification

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXB3	NM_001384749.1	c.-424-5802T>C		intron_variant	Intron 1 of 4	ENST00000498678.6	NP_001371678.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXB3	ENST00000498678.6	c.-424-5802T>C		intron_variant	Intron 1 of 4	2	NM_001384749.1	ENSP00000420595.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000327 AC: 1 AN: 305656 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 175788

African (AFR) AF: 0.00 AC: 0 AN: 5810

American (AMR) AF: 0.00 AC: 0 AN: 22916

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9710

East Asian (EAS) AF: 0.00 AC: 0 AN: 9344

South Asian (SAS) AF: 0.0000183 AC: 1 AN: 54524

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1624

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 159436

Other (OTH) AF: 0.00 AC: 0 AN: 13140

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.1
DANN	Benign	0.47
PhyloP100		0.061
PromoterAI		-0.041	Neutral

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

Other links and lift over

dbSNP: rs3809783; hg19: chr17-46657178;