Variant 5-143820488-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 11/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.26 ( 5235 hom., cov: 31)

Exomes 𝑓: 0.23 ( 41941 hom. )

Consequence

HMHB1
NM_021182.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.313

Variant links:

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]

HMHB1 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMHB1	NM_021182.3 linkuse as main transcript	c.46C>T	p.His16Tyr	missense_variant	2/2	ENST00000289448.4	NP_067005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMHB1	ENST00000289448.4 linkuse as main transcript	c.46C>T	p.His16Tyr	missense_variant	2/2	1	NM_021182.3	ENSP00000289448	P1
	ENST00000503323.1 linkuse as main transcript	n.380-7839C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

38859

AN:

151554

Hom.:

5221

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.272

AC:

67754

AN:

249418

Hom.:

10152

AF XY:

0.262

AC XY:

35465

AN XY:

135316

show subpopulations

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 SAS exome

AF:

0.221

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.:

AF XY:

0.233

AC XY:

167858

AN XY:

720578

show subpopulations

Gnomad4 AFR exome

AF:

0.260

Gnomad4 AMR exome

AF:

0.404

Gnomad4 ASJ exome

AF:

0.267

Gnomad4 EAS exome

AF:

0.413

Gnomad4 SAS exome

AF:

0.218

Gnomad4 FIN exome

AF:

0.256

Gnomad4 NFE exome

AF:

0.219

Gnomad4 OTH exome

AF:

0.239

GnomAD4 genome

AF:

0.256

AC:

38892

AN:

151672

Hom.:

5235

Cov.:

AF XY:

0.259

AC XY:

19155

AN XY:

74082

show subpopulations

Gnomad4 AFR

AF:

0.271

Gnomad4 AMR

AF:

0.323

Gnomad4 ASJ

AF:

0.273

Gnomad4 EAS

AF:

0.397

Gnomad4 SAS

AF:

0.223

Gnomad4 FIN

AF:

0.252

Gnomad4 NFE

AF:

0.223

Gnomad4 OTH

AF:

0.243

Alfa

AF:

0.237

Hom.:

11018

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.67

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

LIST_S2

Benign

0.47

T;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-0.96

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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over