17-75776919-C-T

Position:

• chr17-75776919-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005324.5(H3-3B):​c.*1676G>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 0.648 in 152,136 control chromosomes in the GnomAD database, including 34,268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (34267 hom., cov: 33)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: H3-3B NM_005324.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.393

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 17-75776919-C-T is Benign according to our data. Variant chr17-75776919-C-T is described in ClinVar as [Benign]. Clinvar id is 1227956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
H3-3B	NM_005324.5	c.*1676G>A		3_prime_UTR_variant	4/4	ENST00000254810.8	NP_005315.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
H3-3B	ENST00000254810	c.*1676G>A		3_prime_UTR_variant	4/4	1	NM_005324.5	ENSP00000254810.3

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98516 AN: 152014 Hom.: 34214 Cov.: 33

Gnomad AFR AF: 0.913

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.668

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.750 AC XY: 3 AN XY: 4

Gnomad4 FIN exome AF: 0.500

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.648 AC: 98619 AN: 152132 Hom.: 34267 Cov.: 33 AF XY: 0.641 AC XY: 47653 AN XY: 74360

Gnomad4 AFR AF: 0.913

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.717

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.575

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.667

Alfa AF: 0.583 Hom.: 24771

Bravo AF: 0.671

Asia WGS AF: 0.598 AC: 2082 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	Jul 13, 2018	This variant is associated with the following publications: (PMID: 29529098) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.74
DANN	Benign	0.58

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: rs1060120; hg19: chr17-73773000;