rs61585154

Variant names:

• chr17-48596256-G-A
• rs61585154
• NM_018952.5:c.*157C>T

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.*157C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 1,138,702 control chromosomes in the GnomAD database, including 686 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (158 hom., cov: 32)
  • Exomes 𝑓: 0.028 (528 hom.)
• Consequence: HOXB6 NM_018952.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.48
• Publications: 2 publications found

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=-0.65).
• BP6: Variant 17-48596256-G-A is Benign according to our data. Variant chr17-48596256-G-A is described in ClinVar as [Benign]. Clinvar id is 1258001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXB6	NM_018952.5	c.*157C>T		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.*157C>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_018952.5	ENSP00000225648.3

Frequencies

GnomAD3 genomes AF: 0.0380 AC: 5790 AN: 152204 Hom.: 158 Cov.: 32

Gnomad AFR AF: 0.0709

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0298

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.00376

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0312

Gnomad OTH AF: 0.0463

GnomAD4 exome AF: 0.0281 AC: 27753 AN: 986380 Hom.: 528 Cov.: 13 AF XY: 0.0271 AC XY: 13808 AN XY: 508736

African (AFR) AF: 0.0751 AC: 1835 AN: 24434

American (AMR) AF: 0.0213 AC: 912 AN: 42754

Ashkenazi Jewish (ASJ) AF: 0.0272 AC: 612 AN: 22532

East Asian (EAS) AF: 0.0000534 AC: 2 AN: 37430

South Asian (SAS) AF: 0.00562 AC: 423 AN: 75322

European-Finnish (FIN) AF: 0.00428 AC: 175 AN: 40930

Middle Eastern (MID) AF: 0.0185 AC: 89 AN: 4802

European-Non Finnish (NFE) AF: 0.0323 AC: 22406 AN: 693172

Other (OTH) AF: 0.0289 AC: 1299 AN: 45004

GnomAD4 genome AF: 0.0381 AC: 5802 AN: 152322 Hom.: 158 Cov.: 32 AF XY: 0.0356 AC XY: 2653 AN XY: 74484

African (AFR) AF: 0.0710 AC: 2953 AN: 41566

American (AMR) AF: 0.0297 AC: 454 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 83 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5174

South Asian (SAS) AF: 0.00414 AC: 20 AN: 4832

European-Finnish (FIN) AF: 0.00376 AC: 40 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0312 AC: 2124 AN: 68024

Other (OTH) AF: 0.0458 AC: 97 AN: 2116

Alfa AF: 0.0340 Hom.: 20

Bravo AF: 0.0423

Asia WGS AF: 0.00982 AC: 34 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

- -

Jun 20, 2021

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	-0.65
CADD	Benign	15
DANN	Benign	0.90
PhyloP100		1.5
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: rs61585154; hg19: chr17-46673618;