Genetic Variant H1-0:c.*416T>C (chr22-37806545-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005318.4(H1-0):c.*416T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 185,196 control chromosomes in the GnomAD database, including 67,815 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 0.84 ( 54511 hom., cov: 30)

Exomes 𝑓: 0.89 ( 13304 hom. )

Consequence

H1-0
NM_005318.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0960

Publications

30 publications found

Variant links:

Genes affected

H1-0 (HGNC:4714): (H1.0 linker histone) Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Nucleosomes consist of approximately 146 bp of DNA wrapped around a histone octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. This gene is intronless and encodes a replication-independent histone that is a member of the histone H1 family. [provided by RefSeq, Oct 2015]

H1-0 links:

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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=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
H1-0	NM_005318.4 link	c.*416T>C		3_prime_UTR_variant	Exon 1 of 1	ENST00000340857.4	NP_005309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
H1-0	ENST00000340857.4 link	c.*416T>C		3_prime_UTR_variant	Exon 1 of 1	6	NM_005318.4	ENSP00000344504.2

Frequencies

GnomAD3 genomes

AF:

0.844

AC:

128279

AN:

151932

Hom.:

54478

Cov.:

show subpopulations

Gnomad AFR

AF:

0.754

Gnomad AMI

AF:

0.819

Gnomad AMR

AF:

0.893

Gnomad ASJ

AF:

0.838

Gnomad EAS

AF:

0.993

Gnomad SAS

AF:

0.905

Gnomad FIN

AF:

0.907

Gnomad MID

AF:

0.826

Gnomad NFE

AF:

0.863

Gnomad OTH

AF:

0.853

GnomAD4 exome

AF:

0.895

AC:

29657

AN:

33146

Hom.:

13304

Cov.:

AF XY:

0.895

AC XY:

15373

AN XY:

17186

show subpopulations

African (AFR)

AF:

0.776

AC:

132

AN:

170

American (AMR)

AF:

0.921

AC:

2421

AN:

2628

Ashkenazi Jewish (ASJ)

AF:

0.854

AC:

164

AN:

192

East Asian (EAS)

AF:

0.997

AC:

664

AN:

666

South Asian (SAS)

AF:

0.900

AC:

2604

AN:

2892

European-Finnish (FIN)

AF:

0.910

AC:

13691

AN:

15052

Middle Eastern (MID)

AF:

0.909

AC:

AN:

European-Non Finnish (NFE)

AF:

0.863

AC:

9270

AN:

10740

Other (OTH)

AF:

0.881

AC:

691

AN:

784

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

161

323

484

646

807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

134

268

402

536

670

<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:

0.844

AC:

128368

AN:

152050

Hom.:

54511

Cov.:

AF XY:

0.848

AC XY:

63032

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.754

AC:

31227

AN:

41420

American (AMR)

AF:

0.893

AC:

13640

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.838

AC:

2907

AN:

3470

East Asian (EAS)

AF:

0.993

AC:

5142

AN:

5176

South Asian (SAS)

AF:

0.905

AC:

4356

AN:

4814

European-Finnish (FIN)

AF:

0.907

AC:

9605

AN:

10594

Middle Eastern (MID)

AF:

0.837

AC:

246

AN:

294

European-Non Finnish (NFE)

AF:

0.863

AC:

58697

AN:

67994

Other (OTH)

AF:

0.854

AC:

1803

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1009

2018

3027

4036

5045

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<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:

0.856

Hom.:

109130

Bravo

AF:

0.840

Asia WGS

AF:

0.937

AC:

3258

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

8.8

(source)

DANN

Benign

0.63

PhyloP100

0.096

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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