chr3-129546427-T-G

Variant names:

• chr3-129546427-T-G
• rs2625956
• NM_153833.3:c.89-964T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153833.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H1-8	NM_153833.3	MANE Select	c.89-964T>G		intron	N/A	NP_722575.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H1-8	ENST00000324382.7	TSL:1 MANE Select	c.89-964T>G		intron	N/A	ENSP00000319799.2

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

African (AFR) AF: 0.799 AC: 33131 AN: 41480

American (AMR) AF: 0.337 AC: 5155 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1024 AN: 3468

East Asian (EAS) AF: 0.633 AC: 3282 AN: 5188

South Asian (SAS) AF: 0.372 AC: 1793 AN: 4816

European-Finnish (FIN) AF: 0.0726 AC: 770 AN: 10612

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.164 AC: 11179 AN: 68002

Other (OTH) AF: 0.343 AC: 722 AN: 2106

Alfa AF: 0.233 Hom.: 10003

Bravo AF: 0.415

Asia WGS AF: 0.498 AC: 1735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.3
DANN	Benign	0.45
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2625956; hg19: chr3-129265270;