17-48596362-C-T

Variant names:

• chr17-48596362-C-T
• rs12940530
• NM_018952.5:c.*51G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018952.5(HOXB6):​c.*51G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,612,892 control chromosomes in the GnomAD database, including 255,543 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (18152 hom., cov: 32)
  • Exomes 𝑓: 0.57 (237391 hom.)
• Consequence: HOXB6 NM_018952.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.604

Genes affected

HOXB6 (HGNC:5117): (homeobox B6) This gene is a member of the Antp homeobox family and encodes a 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, including that of lung and skin, and has been localized to both the nucleus and cytoplasm. Altered expression of this gene or a change in the subcellular localization of its protein is associated with some cases of acute myeloid leukemia and colorectal cancer. [provided by RefSeq, Jul 2008]

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

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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-48596362-C-T is Benign according to our data. Variant chr17-48596362-C-T is described in ClinVar as [Benign]. Clinvar id is 1296776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXB6	NM_018952.5	c.*51G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000225648.4	NP_061825.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXB6	ENST00000225648.4	c.*51G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_018952.5	ENSP00000225648.3

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69270 AN: 151684 Hom.: 18149 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.501

GnomAD2 exomes AF: 0.534 AC: 133854 AN: 250566 AF XY: 0.542

Gnomad AFR exome AF: 0.161

Gnomad AMR exome AF: 0.572

Gnomad ASJ exome AF: 0.550

Gnomad EAS exome AF: 0.498

Gnomad FIN exome AF: 0.593

Gnomad NFE exome AF: 0.569

Gnomad OTH exome AF: 0.556

GnomAD4 exome AF: 0.566 AC: 826385 AN: 1461088 Hom.: 237391 Cov.: 38 AF XY: 0.566 AC XY: 411658 AN XY: 726870

African (AFR) AF: 0.155 AC: 5198 AN: 33472

American (AMR) AF: 0.571 AC: 25546 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 14238 AN: 26128

East Asian (EAS) AF: 0.554 AC: 21989 AN: 39692

South Asian (SAS) AF: 0.535 AC: 46074 AN: 86190

European-Finnish (FIN) AF: 0.583 AC: 31025 AN: 53258

Middle Eastern (MID) AF: 0.563 AC: 3246 AN: 5766

European-Non Finnish (NFE) AF: 0.581 AC: 646182 AN: 1111482

Other (OTH) AF: 0.545 AC: 32887 AN: 60376

GnomAD4 genome AF: 0.456 AC: 69287 AN: 151804 Hom.: 18152 Cov.: 32 AF XY: 0.459 AC XY: 34050 AN XY: 74198

African (AFR) AF: 0.173 AC: 7164 AN: 41500

American (AMR) AF: 0.548 AC: 8356 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1887 AN: 3466

East Asian (EAS) AF: 0.520 AC: 2674 AN: 5138

South Asian (SAS) AF: 0.510 AC: 2462 AN: 4826

European-Finnish (FIN) AF: 0.586 AC: 6163 AN: 10526

Middle Eastern (MID) AF: 0.538 AC: 157 AN: 292

European-Non Finnish (NFE) AF: 0.574 AC: 38895 AN: 67786

Other (OTH) AF: 0.502 AC: 1058 AN: 2106

Alfa AF: 0.534 Hom.: 4897

Bravo AF: 0.443

Asia WGS AF: 0.488 AC: 1700 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.2
DANN	Benign	0.89
PhyloP100		-0.60
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

Publications

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Other links and lift over

dbSNP: rs12940530; hg19: chr17-46673724; COSMIC: COSV53312071; COSMIC: COSV53312071;