chr17-48567980-T-C

Variant names:

• chr17-48567980-T-C
• rs4646992
• NM_001384749.1:c.-247+5857A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384749.1(HOXB3):​c.-247+5857A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 152,104 control chromosomes in the GnomAD database, including 55,549 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 0.85 (55549 hom., cov: 31)
• Consequence: HOXB3 NM_001384749.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159
• Publications: 1 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]

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXB3	NM_001384749.1	MANE Select	c.-247+5857A>G		intron	N/A	NP_001371678.1
	HOXB3	NM_001384747.1		c.-13-15493A>G		intron	N/A	NP_001371676.1
	HOXB3	NM_002146.4		c.-247+5857A>G		intron	N/A	NP_002137.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXB3	ENST00000498678.6	TSL:2 MANE Select	c.-247+5857A>G		intron	N/A	ENSP00000420595.1
	HOXB3	ENST00000311626.8	TSL:1	c.-247+5857A>G		intron	N/A	ENSP00000308252.4
	HOXB3	ENST00000476342.1	TSL:1	c.-13-15493A>G		intron	N/A	ENSP00000418892.1

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129402 AN: 151986 Hom.: 55500 Cov.: 31

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.878

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.903

Gnomad OTH AF: 0.867

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.851 AC: 129501 AN: 152104 Hom.: 55549 Cov.: 31 AF XY: 0.850 AC XY: 63182 AN XY: 74366

African (AFR) AF: 0.753 AC: 31187 AN: 41418

American (AMR) AF: 0.842 AC: 12880 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.878 AC: 3046 AN: 3468

East Asian (EAS) AF: 0.858 AC: 4437 AN: 5170

South Asian (SAS) AF: 0.764 AC: 3687 AN: 4824

European-Finnish (FIN) AF: 0.942 AC: 9980 AN: 10596

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.903 AC: 61420 AN: 68006

Other (OTH) AF: 0.868 AC: 1834 AN: 2112

Alfa AF: 0.896 Hom.: 26469

Bravo AF: 0.843

Asia WGS AF: 0.779 AC: 2709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.1
DANN	Benign	0.49
PhyloP100		-0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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

Other links and lift over

dbSNP: rs4646992; hg19: chr17-46645342;