rs1414280

Positions:

• chr6-79219013-C-A
• chr6-79219013-C-G

Variant summary

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

The ENST00000620514.2(HMGN3):​c.16-3991G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 151,878 control chromosomes in the GnomAD database, including 19,711 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 0.49 (19711 hom., cov: 32)
• Consequence: HMGN3 ENST00000620514.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.877

Genes affected

HMGN3 (HGNC:12312): (high mobility group nucleosomal binding domain 3) The protein encoded by this gene binds thyroid hormone receptor beta in the presence of thyroid hormone. The encoded protein, a member of the HMGN protein family, is thought to reduce the compactness of the chromatin fiber in nucleosomes, thereby enhancing transcription from chromatin templates. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. There is a related pseudogene on chromosome 1. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMGN3	NM_001201363.2	c.16-3991G>T		intron_variant		ENST00000620514.2
HMGN3	NM_001318885.2	c.16-10437G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGN3	ENST00000620514.2	c.16-3991G>T		intron_variant		3	NM_001201363.2

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74618 AN: 151760 Hom.: 19704 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.491 AC: 74641 AN: 151878 Hom.: 19711 Cov.: 32 AF XY: 0.496 AC XY: 36844 AN XY: 74232

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.798

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.549

Alfa AF: 0.496 Hom.: 4254

Bravo AF: 0.498

Asia WGS AF: 0.643 AC: 2233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.64
DANN	Benign	0.39

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: rs1414280; hg19: chr6-79928730; COSMIC: COSV51515458;