17-75778796-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.27

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
H3-3B	NM_005324.5	c.282+14C>T		intron_variant		ENST00000254810.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
H3-3B	ENST00000254810.8	c.282+14C>T		intron_variant		1	NM_005324.5	P1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25663 AN: 152042 Hom.: 2459 Cov.: 32

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

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.: 32 AF XY: 0.146 AC XY: 106012 AN XY: 727214

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.: 32 AF XY: 0.167 AC XY: 12420 AN XY: 74390

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	0.053
Dann	Benign	0.86
FATHMM_MKL	Benign	0.0086	N
LIST_S2	Benign	0.31	T
MetaRNN	Benign	0.0052	T
MutationTaster	Benign	1.0	P;P;P;P;P;P
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

Other links and lift over

dbSNP: rs9895763; hg19: chr17-73774877; COSMIC: COSV54666007; COSMIC: COSV54666007;