Genetic Variant NM_002729.5:c.541-29T>G (chr10-92692673-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002729.5(HHEX):c.541-29T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,612,120 control chromosomes in the GnomAD database, including 10,023 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 0.11 ( 1050 hom., cov: 32)

Exomes 𝑓: 0.11 ( 8973 hom. )

Consequence

HHEX
NM_002729.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.241

Publications

18 publications found

Variant links:

Genes affected

HHEX (HGNC:4901): (hematopoietically expressed homeobox) This gene encodes a member of the homeobox family of transcription factors, many of which are involved in developmental processes. Expression in specific hematopoietic lineages suggests that this protein may play a role in hematopoietic differentiation. [provided by RefSeq, Jul 2008]

HHEX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HHEX	NM_002729.5 link	c.541-29T>G		intron_variant	Intron 2 of 3	ENST00000282728.10	NP_002720.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
HHEX	ENST00000282728.10 link	c.541-29T>G	intron_variant	Intron 2 of 3	1	NM_002729.5	ENSP00000282728.5
HHEX	ENST00000492654.3 link	c.25-29T>G	intron_variant	Intron 1 of 2	1		ENSP00000447953.1
HHEX	ENST00000472590.6 link	c.25-29T>G	intron_variant	Intron 2 of 3	2		ENSP00000450017.1
HHEX	ENST00000551454.1 link	n.*190T>G	downstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17090

AN:

151558

Hom.:

1050

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.206

Gnomad AMR

AF:

0.120

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.0421

Gnomad SAS

AF:

0.0513

Gnomad FIN

AF:

0.0545

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.113

GnomAD2 exomes

AF:

0.0978

AC:

24503

AN:

250624

AF XY:

0.0948

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.107

Gnomad ASJ exome

AF:

0.222

Gnomad EAS exome

AF:

0.0514

Gnomad FIN exome

AF:

0.0581

Gnomad NFE exome

AF:

0.106

Gnomad OTH exome

AF:

0.107

GnomAD4 exome

AF:

0.106

AC:

155297

AN:

1460444

Hom.:

8973

Cov.:

AF XY:

0.105

AC XY:

76315

AN XY:

726582

show subpopulations

African (AFR)

AF:

0.127

AC:

4249

AN:

33456

American (AMR)

AF:

0.107

AC:

4805

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.220

AC:

5758

AN:

26128

East Asian (EAS)

AF:

0.0423

AC:

1678

AN:

39698

South Asian (SAS)

AF:

0.0539

AC:

4645

AN:

86242

European-Finnish (FIN)

AF:

0.0591

AC:

3122

AN:

52842

Middle Eastern (MID)

AF:

0.129

AC:

743

AN:

5764

European-Non Finnish (NFE)

AF:

0.111

AC:

123391

AN:

1111246

Other (OTH)

AF:

0.114

AC:

6906

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

7168

14336

21504

28672

35840

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4520

9040

13560

18080

22600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.113

AC:

17109

AN:

151676

Hom.:

1050

Cov.:

AF XY:

0.109

AC XY:

8051

AN XY:

74088

show subpopulations

African (AFR)

AF:

0.131

AC:

5435

AN:

41336

American (AMR)

AF:

0.120

AC:

1825

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

818

AN:

3470

East Asian (EAS)

AF:

0.0420

AC:

214

AN:

5098

South Asian (SAS)

AF:

0.0511

AC:

246

AN:

4812

European-Finnish (FIN)

AF:

0.0545

AC:

572

AN:

10496

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.111

AC:

7543

AN:

67930

Other (OTH)

AF:

0.112

AC:

236

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

749

1497

2246

2994

3743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.114

Hom.:

1648

Bravo

AF:

0.119

Asia WGS

AF:

0.0570

AC:

201

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

9.0

(source)

DANN

Benign

0.54

PhyloP100

-0.24

Mutation Taster

=100/0

polymorphism (auto)

(source)

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over