rs1414280

Variant names:

• chr6-79219013-C-A
• rs1414280
• NM_001201363.2:c.16-3991G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_001201363.2(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 NM_001201363.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.877
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001201363.2. 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
	HMGN3	NM_001201363.2	MANE Select	c.16-3991G>T		intron	N/A	NP_001188292.1	A0A087WZE9
	HMGN3	NM_001318887.2		c.16-3991G>T		intron	N/A	NP_001305816.1
	HMGN3	NM_001318886.2		c.16-3991G>T		intron	N/A	NP_001305815.1	A0A994J3W4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGN3	ENST00000620514.2	TSL:3 MANE Select	c.16-3991G>T		intron	N/A	ENSP00000482613.1	A0A087WZE9
	HMGN3	ENST00000344726.10	TSL:1	c.16-3991G>T		intron	N/A	ENSP00000341267.5	Q15651-1
	HMGN3	ENST00000275036.11	TSL:1	c.16-3991G>T		intron	N/A	ENSP00000275036.7	Q15651-2

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

African (AFR) AF: 0.311 AC: 12865 AN: 41392

American (AMR) AF: 0.664 AC: 10142 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1739 AN: 3466

East Asian (EAS) AF: 0.798 AC: 4131 AN: 5174

South Asian (SAS) AF: 0.496 AC: 2386 AN: 4810

European-Finnish (FIN) AF: 0.538 AC: 5671 AN: 10532

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.528 AC: 35856 AN: 67914

Other (OTH) AF: 0.549 AC: 1159 AN: 2110

Alfa AF: 0.463 Hom.: 8323

Bravo AF: 0.498

Asia WGS AF: 0.643 AC: 2233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.64
DANN	Benign	0.39
PhyloP100		-0.88
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: rs1414280; hg19: chr6-79928730; COSMIC: COSV51515458;