rs161557

Variant names:

• chr5-143820488-C-T
• rs161557
• NM_021182.3:c.46C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PM1 BP4_Strong BA1

The NM_021182.3(HMHB1):​c.46C>T​(p.His16Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,598,138 control chromosomes in the GnomAD database, including 47,176 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (5235 hom., cov: 31)
  • Exomes 𝑓: 0.23 (41941 hom.)
• Consequence: HMHB1 NM_021182.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313
• Publications: 29 publications found

Genes affected

HMHB1 (HGNC:29677): (histocompatibility minor HB-1) This gene encodes one of the minor histocompatibility antigens, which play an important role in the induction of cytotoxic T lymphocyte (CTL) reactivity against leukemia after human histocompatibility leukocyte antigen (HLA)-identical allogeneic bone marrow transplantation (BMT). This gene is only expressed in B cell acute lymphoblastic leukemia cells and Epstein-Barr virus-transformed B cells. The translation of this mRNA initiates at a non-AUG (CUG) codon. [provided by RefSeq, Jul 2008]

ENSG00000249881 (HGNC:):

ACMG classification

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

• PM1: In a mutagenesis_site CTL recognition. (size 0) in uniprot entity HMHB1_HUMAN
• BP4: Computational evidence support a benign effect (MetaRNN=0.0018491745).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021182.3. 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
	HMHB1	NM_021182.3	MANE Select	c.46C>T	p.His16Tyr	missense	Exon 2 of 2	NP_067005.1	O97980

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMHB1	ENST00000289448.4	TSL:1 MANE Select	c.46C>T	p.His16Tyr	missense	Exon 2 of 2	ENSP00000289448.3	O97980
	HMHB1	ENST00000850872.1		n.358C>T		non_coding_transcript_exon	Exon 3 of 3
	ENSG00000249881	ENST00000503323.1	TSL:3	n.380-7839C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38859 AN: 151554 Hom.: 5221 Cov.: 31

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.245

GnomAD2 exomes AF: 0.272 AC: 67754 AN: 249418 AF XY: 0.262

Gnomad AFR exome AF: 0.267

Gnomad AMR exome AF: 0.416

Gnomad ASJ exome AF: 0.272

Gnomad EAS exome AF: 0.405

Gnomad FIN exome AF: 0.251

Gnomad NFE exome AF: 0.226

Gnomad OTH exome AF: 0.250

GnomAD4 exome AF: 0.234 AC: 338264 AN: 1446466 Hom.: 41941 Cov.: 28 AF XY: 0.233 AC XY: 167858 AN XY: 720578

African (AFR) AF: 0.260 AC: 8623 AN: 33200

American (AMR) AF: 0.404 AC: 18029 AN: 44616

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 6945 AN: 26006

East Asian (EAS) AF: 0.413 AC: 16335 AN: 39554

South Asian (SAS) AF: 0.218 AC: 18752 AN: 85944

European-Finnish (FIN) AF: 0.256 AC: 13621 AN: 53272

Middle Eastern (MID) AF: 0.161 AC: 924 AN: 5748

European-Non Finnish (NFE) AF: 0.219 AC: 240727 AN: 1098316

Other (OTH) AF: 0.239 AC: 14308 AN: 59810

GnomAD4 genome AF: 0.256 AC: 38892 AN: 151672 Hom.: 5235 Cov.: 31 AF XY: 0.259 AC XY: 19155 AN XY: 74082

African (AFR) AF: 0.271 AC: 11199 AN: 41330

American (AMR) AF: 0.323 AC: 4925 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 948 AN: 3470

East Asian (EAS) AF: 0.397 AC: 2043 AN: 5144

South Asian (SAS) AF: 0.223 AC: 1071 AN: 4800

European-Finnish (FIN) AF: 0.252 AC: 2643 AN: 10490

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.223 AC: 15144 AN: 67890

Other (OTH) AF: 0.243 AC: 513 AN: 2110

Alfa AF: 0.241 Hom.: 15699

Bravo AF: 0.266

TwinsUK AF: 0.214 AC: 793

ALSPAC AF: 0.221 AC: 851

ESP6500AA AF: 0.255 AC: 950

ESP6500EA AF: 0.219 AC: 1797

ExAC AF: 0.265 AC: 32024

Asia WGS AF: 0.296 AC: 1030 AN: 3478

EpiCase AF: 0.218

EpiControl AF: 0.218

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.4
DANN	Benign	0.62
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0036	N
LIST_S2	Benign	0.47	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-0.96	T
PhyloP100		-0.31
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.021	B
ClinPred		0.033	T
GERP RS		-2.3
Varity_R		0.025
gMVP		0.0016

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs161557; hg19: chr5-143200053; COSMIC: COSV56869341;