rs10484434

Variant names:

• chr6-26031385-G-A
• rs10484434
• ENST00000730115.1:n.562-9947G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000730115.1(LINC02980):​n.562-9947G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 151,814 control chromosomes in the GnomAD database, including 1,084 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 0.10 (1084 hom., cov: 29)
• Consequence: LINC02980 ENST00000730115.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430
• Publications: 23 publications found

Genes affected

LINC02980 (HGNC:56046): (long intergenic non-protein coding RNA 2980)

H3C2 (HGNC:4776): (H3 clustered histone 2) Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. This structure consists of approximately 146 bp of DNA wrapped around a nucleosome, an 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. This gene is intronless and encodes a replication-dependent histone that is a member of the histone H3 family. Transcripts from this gene lack polyA tails; instead, they contain a palindromic termination element. This gene is found in the large histone gene cluster on chromosome 6p22-p21.3. [provided by RefSeq, Aug 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000730115.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H3C2	NM_003537.4	MANE Select	c.*265C>T		downstream_gene	N/A	NP_003528.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC02980	ENST00000730115.1		n.562-9947G>A		intron	N/A
	H3C2	ENST00000621411.3	TSL:6 MANE Select	c.*265C>T		downstream_gene	N/A	ENSP00000484841.2	P68431

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15880 AN: 151694 Hom.: 1085 Cov.: 29

Gnomad AFR AF: 0.0322

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.0562

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.105 AC: 15872 AN: 151814 Hom.: 1084 Cov.: 29 AF XY: 0.105 AC XY: 7777 AN XY: 74168

African (AFR) AF: 0.0320 AC: 1327 AN: 41408

American (AMR) AF: 0.112 AC: 1704 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 800 AN: 3468

East Asian (EAS) AF: 0.0564 AC: 290 AN: 5144

South Asian (SAS) AF: 0.180 AC: 865 AN: 4800

European-Finnish (FIN) AF: 0.103 AC: 1082 AN: 10518

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9367 AN: 67934

Other (OTH) AF: 0.127 AC: 266 AN: 2100

Alfa AF: 0.130 Hom.: 4426

Bravo AF: 0.0998

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.1
DANN	Benign	0.24
PhyloP100		-0.043

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10484434; hg19: chr6-26031613;