Variant 17-75778796-G-A 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_005324.5(H3-3B):c.282+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,613,984 control chromosomes in the GnomAD database, including 18,864 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2465 hom., cov: 32)

Exomes 𝑓: 0.14 ( 16399 hom. )

Consequence

H3-3B
NM_005324.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.27

Variant links:

Genes affected

H3-3B (HGNC:4765): (H3.3 histone B) Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene contains introns and its mRNA is polyadenylated, unlike most histone genes. The protein encoded by this gene is a replication-independent histone that is a member of the histone H3 family. Pseudogenes of this gene have been identified on the X chromosome, and on chromosomes 5, 13 and 17. [provided by RefSeq, Oct 2015]

H3-3B links:

H3-3B (HGNC:):

H3-3B 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 (MetaRNN=0.0052175224).

BP6

Variant 17-75778796-G-A is Benign according to our data. Variant chr17-75778796-G-A is described in ClinVar as [Benign]. Clinvar id is 1236882.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
H3-3B	NM_005324.5 linkuse as main transcript	c.282+14C>T		intron_variant		ENST00000254810.8	NP_005315.1	P84243B2R4P9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
H3-3B	ENST00000254810.8 linkuse as main transcript	c.282+14C>T		intron_variant		1	NM_005324.5	ENSP00000254810.3		P84243

Frequencies

GnomAD3 genomes

AF:

0.169

AC:

25663

AN:

152042

Hom.:

2459

Cov.:

show subpopulations

Gnomad AFR

AF:

0.264

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.0114

Gnomad SAS

AF:

0.224

Gnomad FIN

AF:

0.120

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.151

GnomAD3 exomes

AF:

0.141

AC:

35443

AN:

251214

Hom.:

3122

AF XY:

0.148

AC XY:

20076

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.266

Gnomad AMR exome

AF:

0.0712

Gnomad ASJ exome

AF:

0.195

Gnomad EAS exome

AF:

0.00560

Gnomad SAS exome

AF:

0.245

Gnomad FIN exome

AF:

0.114

Gnomad NFE exome

AF:

0.138

Gnomad OTH exome

AF:

0.146

GnomAD4 exome

AF:

0.142

AC:

207978

AN:

1461824

Hom.:

16399

Cov.:

AF XY:

0.146

AC XY:

106012

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.276

Gnomad4 AMR exome

AF:

0.0759

Gnomad4 ASJ exome

AF:

0.193

Gnomad4 EAS exome

AF:

0.0184

Gnomad4 SAS exome

AF:

0.245

Gnomad4 FIN exome

AF:

0.116

Gnomad4 NFE exome

AF:

0.137

Gnomad4 OTH exome

AF:

0.151

GnomAD4 genome

AF:

0.169

AC:

25698

AN:

152160

Hom.:

2465

Cov.:

AF XY:

0.167

AC XY:

12420

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.264

Gnomad4 AMR

AF:

0.111

Gnomad4 ASJ

AF:

0.189

Gnomad4 EAS

AF:

0.0114

Gnomad4 SAS

AF:

0.225

Gnomad4 FIN

AF:

0.120

Gnomad4 NFE

AF:

0.140

Gnomad4 OTH

AF:

0.151

Alfa

AF:

0.136

Hom.:

1733

Bravo

AF:

0.169

TwinsUK

AF:

0.132

AC:

488

ALSPAC

AF:

0.141

AC:

544

ESP6500AA

AF:

0.253

AC:

1114

ESP6500EA

AF:

0.144

AC:

1236

ExAC

AF:

0.147

AC:

17815

Asia WGS

AF:

0.138

AC:

482

AN:

3478

EpiCase

AF:

0.150

EpiControl

AF:

0.148

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.053

DANN

Benign

0.86

FATHMM_MKL

Benign

0.0086

LIST_S2

Benign

0.31

MetaRNN

Benign

0.0052

GERP RS

-10

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

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