17-48596177-C-T

Variant names:

• chr17-48596177-C-T
• rs72829881
• NM_018952.5:c.*236G>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.*236G>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 0.0608 in 696,066 control chromosomes in the GnomAD database, including 1,615 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.053 (277 hom., cov: 32)
  • Exomes 𝑓: 0.063 (1338 hom.)
• Consequence: HOXB6 NM_018952.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.570

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=-0.81).
• BP6: Variant 17-48596177-C-T is Benign according to our data. Variant chr17-48596177-C-T is described in ClinVar as [Benign]. Clinvar id is 1288313.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXB6	NM_018952.5	c.*236G>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.*236G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_018952.5	ENSP00000225648.3

Frequencies

GnomAD3 genomes AF: 0.0528 AC: 8035 AN: 152204 Hom.: 275 Cov.: 32

Gnomad AFR AF: 0.0140

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0330

Gnomad ASJ AF: 0.0377

Gnomad EAS AF: 0.0175

Gnomad SAS AF: 0.0719

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0741

Gnomad OTH AF: 0.0445

GnomAD4 exome AF: 0.0631 AC: 34291 AN: 543744 Hom.: 1338 Cov.: 5 AF XY: 0.0642 AC XY: 18890 AN XY: 294396

African (AFR) AF: 0.0129 AC: 202 AN: 15670

American (AMR) AF: 0.0264 AC: 906 AN: 34294

Ashkenazi Jewish (ASJ) AF: 0.0315 AC: 618 AN: 19632

East Asian (EAS) AF: 0.00663 AC: 205 AN: 30902

South Asian (SAS) AF: 0.0657 AC: 4106 AN: 62516

European-Finnish (FIN) AF: 0.112 AC: 3569 AN: 31932

Middle Eastern (MID) AF: 0.0248 AC: 100 AN: 4032

European-Non Finnish (NFE) AF: 0.0729 AC: 22945 AN: 314864

Other (OTH) AF: 0.0548 AC: 1640 AN: 29902

GnomAD4 genome AF: 0.0528 AC: 8042 AN: 152322 Hom.: 277 Cov.: 32 AF XY: 0.0538 AC XY: 4006 AN XY: 74470

African (AFR) AF: 0.0140 AC: 582 AN: 41594

American (AMR) AF: 0.0329 AC: 503 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0377 AC: 131 AN: 3472

East Asian (EAS) AF: 0.0172 AC: 89 AN: 5182

South Asian (SAS) AF: 0.0728 AC: 351 AN: 4824

European-Finnish (FIN) AF: 0.112 AC: 1185 AN: 10612

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0741 AC: 5040 AN: 68016

Other (OTH) AF: 0.0473 AC: 100 AN: 2114

Alfa AF: 0.0699 Hom.: 194

Bravo AF: 0.0443

Asia WGS AF: 0.0470 AC: 163 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.90
PhyloP100		-0.57
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: rs72829881; hg19: chr17-46673539;