Variant chr22-19331389-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003325.4(HIRA):c.*51G>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 0.00911 in 1,610,926 control chromosomes in the GnomAD database, including 289 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 27 hom., cov: 33)

Exomes 𝑓: 0.0093 ( 262 hom. )

Consequence

HIRA
NM_003325.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.96

Variant links:

Genes affected

HIRA (HGNC:4916): (histone cell cycle regulator) This gene encodes a histone chaperone that preferentially places the variant histone H3.3 in nucleosomes. Orthologs of this gene in yeast, flies, and plants are necessary for the formation of transcriptionally silent heterochomatin. This gene plays an important role in the formation of the senescence-associated heterochromatin foci. These foci likely mediate the irreversible cell cycle changes that occur in senescent cells. It is considered the primary candidate gene in some haploinsufficiency syndromes such as DiGeorge syndrome, and insufficient production of the gene may disrupt normal embryonic development. [provided by RefSeq, Jul 2008]

HIRA links:

LOC105372859 (HGNC:):

LOC105372859 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 22-19331389-C-T is Benign according to our data. Variant chr22-19331389-C-T is described in ClinVar as [Benign]. Clinvar id is 1246924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
HIRA	NM_003325.4 linkuse as main transcript	c.*51G>A	3_prime_UTR_variant	25/25	ENST00000263208.5	NP_003316.3	P54198-1
LOC105372859	XR_938000.3 linkuse as main transcript	n.561-165C>T	intron_variant
LOC105372859	XR_938001.3 linkuse as main transcript	n.561-165C>T	intron_variant
LOC105372859	XR_938002.3 linkuse as main transcript	n.667-165C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIRA	ENST00000263208 linkuse as main transcript	c.*51G>A		3_prime_UTR_variant	25/25	1	NM_003325.4	ENSP00000263208.5		P54198-1
HIRA	ENST00000340170 linkuse as main transcript	c.*51G>A		3_prime_UTR_variant	21/21	1		ENSP00000345350.4		P54198-2

Frequencies

GnomAD3 genomes

AF:

0.00760

AC:

1157

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.0239

Gnomad EAS

AF:

0.0684

Gnomad SAS

AF:

0.0437

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.00522

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.0139

AC:

3451

AN:

247714

Hom.:

AF XY:

0.0151

AC XY:

2023

AN XY:

134194

show subpopulations

Gnomad AFR exome

AF:

0.000928

Gnomad AMR exome

AF:

0.00229

Gnomad ASJ exome

AF:

0.0250

Gnomad EAS exome

AF:

0.0700

Gnomad SAS exome

AF:

0.0363

Gnomad FIN exome

AF:

0.000152

Gnomad NFE exome

AF:

0.00554

Gnomad OTH exome

AF:

0.0141

GnomAD4 exome

AF:

0.00927

AC:

13520

AN:

1458628

Hom.:

262

Cov.:

AF XY:

0.0101

AC XY:

7359

AN XY:

725678

show subpopulations

Gnomad4 AFR exome

AF:

0.00143

Gnomad4 AMR exome

AF:

0.00251

Gnomad4 ASJ exome

AF:

0.0254

Gnomad4 EAS exome

AF:

0.0776

Gnomad4 SAS exome

AF:

0.0366

Gnomad4 FIN exome

AF:

0.000236

Gnomad4 NFE exome

AF:

0.00492

Gnomad4 OTH exome

AF:

0.0129

GnomAD4 genome

AF:

0.00761

AC:

1159

AN:

152298

Hom.:

Cov.:

AF XY:

0.00835

AC XY:

622

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000914

Gnomad4 AMR

AF:

0.00359

Gnomad4 ASJ

AF:

0.0239

Gnomad4 EAS

AF:

0.0686

Gnomad4 SAS

AF:

0.0439

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00522

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.00649

Hom.:

Bravo

AF:

0.00678

Asia WGS

AF:

0.0390

AC:

136

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.063

DANN

Benign

0.42

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over