rs2625956

Positions:

• chr3-129546427-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153833.3(H1-8):​c.89-964T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,166 control chromosomes in the GnomAD database, including 16,920 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 0.38 (16920 hom., cov: 32)
• Consequence: H1-8 NM_153833.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234

Genes affected

H1-8 (HGNC:18463): (H1.8 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. The protein encoded is a replication-independent histone that is a member of the histone H1 family. This gene contains introns, unlike most histone genes. The related mouse gene is expressed only in oocytes. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
H1-8	NM_153833.3	c.89-964T>G		intron_variant		ENST00000324382.7	NP_722575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
H1-8	ENST00000324382.7	c.89-964T>G		intron_variant		1	NM_153833.3	ENSP00000319799	P1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57157 AN: 152050 Hom.: 16859 Cov.: 32

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.0726

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.342

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.376 AC: 57279 AN: 152166 Hom.: 16920 Cov.: 32 AF XY: 0.376 AC XY: 27992 AN XY: 74416

Gnomad4 AFR AF: 0.799

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.0726

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.343

Alfa AF: 0.214 Hom.: 6129

Bravo AF: 0.415

Asia WGS AF: 0.498 AC: 1735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.3
DANN	Benign	0.45

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: rs2625956; hg19: chr3-129265270;