17-48542733-G-T

Variant names:

• chr17-48542733-G-T
• rs1042822
• NM_002145.4:c.*335C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002145.4(HOXB2):​c.*335C>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 0.158 in 190,770 control chromosomes in the GnomAD database, including 2,678 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 0.16 (2080 hom., cov: 32)
  • Exomes 𝑓: 0.16 (598 hom.)
• Consequence: HOXB2 NM_002145.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.00
• Publications: 13 publications found

Genes affected

HOXB2 (HGNC:5113): (homeobox B2) 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 pancreatic cancer. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002145.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXB2	NM_002145.4	MANE Select	c.*335C>A		3_prime_UTR	Exon 2 of 2	NP_002136.1	P14652

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXB2	ENST00000330070.6	TSL:1 MANE Select	c.*335C>A		3_prime_UTR	Exon 2 of 2	ENSP00000331741.4	P14652
	HOXB2	ENST00000504772.3	TSL:3	n.192+222C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23785 AN: 152046 Hom.: 2079 Cov.: 32

Gnomad AFR AF: 0.0812

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0859

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.168

GnomAD4 exome AF: 0.163 AC: 6285 AN: 38606 Hom.: 598 Cov.: 0 AF XY: 0.163 AC XY: 3221 AN XY: 19728

African (AFR) AF: 0.0717 AC: 118 AN: 1646

American (AMR) AF: 0.137 AC: 170 AN: 1240

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 290 AN: 1702

East Asian (EAS) AF: 0.0392 AC: 113 AN: 2882

South Asian (SAS) AF: 0.120 AC: 45 AN: 374

European-Finnish (FIN) AF: 0.205 AC: 377 AN: 1836

Middle Eastern (MID) AF: 0.205 AC: 45 AN: 220

European-Non Finnish (NFE) AF: 0.182 AC: 4739 AN: 26044

Other (OTH) AF: 0.146 AC: 388 AN: 2662

GnomAD4 genome AF: 0.156 AC: 23790 AN: 152164 Hom.: 2080 Cov.: 32 AF XY: 0.157 AC XY: 11681 AN XY: 74396

African (AFR) AF: 0.0813 AC: 3377 AN: 41524

American (AMR) AF: 0.156 AC: 2385 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 634 AN: 3464

East Asian (EAS) AF: 0.0855 AC: 444 AN: 5190

South Asian (SAS) AF: 0.131 AC: 634 AN: 4824

European-Finnish (FIN) AF: 0.223 AC: 2352 AN: 10568

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13294 AN: 67982

Other (OTH) AF: 0.165 AC: 349 AN: 2114

Alfa AF: 0.175 Hom.: 473

Bravo AF: 0.148

Asia WGS AF: 0.131 AC: 454 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	17
DANN	Benign	0.84
PhyloP100		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
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: rs1042822; hg19: chr17-46620095;