rs4871

Variant names:

• chr6-26545404-G-A
• rs4871
• NM_006353.3:c.198G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006353.3(HMGN4):​c.198G>A​(p.Gly66Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 1,612,440 control chromosomes in the GnomAD database, including 194,442 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 0.50 (19436 hom., cov: 31)
  • Exomes 𝑓: 0.49 (175006 hom.)
• Consequence: HMGN4 NM_006353.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190
• Publications: 39 publications found

Genes affected

HMGN4 (HGNC:4989): (high mobility group nucleosomal binding domain 4) The protein encoded by this gene, 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. [provided by RefSeq, Mar 2013]

ENSG00000291336 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=-0.19 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGN4	NM_006353.3	c.198G>A	p.Gly66Gly	synonymous_variant	Exon 2 of 2	ENST00000377575.3	NP_006344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMGN4	ENST00000377575.3	c.198G>A	p.Gly66Gly	synonymous_variant	Exon 2 of 2	1	NM_006353.3	ENSP00000366798.1
ENSG00000291336	ENST00000707189.1	n.1000-7783G>A		intron_variant	Intron 1 of 1
ENSG00000300261	ENST00000770465.1	n.502+2754C>T		intron_variant	Intron 2 of 2
ENSG00000300261	ENST00000770466.1	n.241+2754C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76268 AN: 151818 Hom.: 19416 Cov.: 31

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.512

GnomAD2 exomes AF: 0.516 AC: 129030 AN: 250300 AF XY: 0.510

Gnomad AFR exome AF: 0.523

Gnomad AMR exome AF: 0.592

Gnomad ASJ exome AF: 0.567

Gnomad EAS exome AF: 0.755

Gnomad FIN exome AF: 0.403

Gnomad NFE exome AF: 0.465

Gnomad OTH exome AF: 0.502

GnomAD4 exome AF: 0.486 AC: 709935 AN: 1460506 Hom.: 175006 Cov.: 41 AF XY: 0.486 AC XY: 352979 AN XY: 726576

African (AFR) AF: 0.510 AC: 16976 AN: 33306

American (AMR) AF: 0.586 AC: 26036 AN: 44400

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 14583 AN: 26082

East Asian (EAS) AF: 0.734 AC: 29149 AN: 39688

South Asian (SAS) AF: 0.529 AC: 45515 AN: 86108

European-Finnish (FIN) AF: 0.411 AC: 21960 AN: 53368

Middle Eastern (MID) AF: 0.491 AC: 2825 AN: 5758

European-Non Finnish (NFE) AF: 0.470 AC: 522066 AN: 1111480

Other (OTH) AF: 0.511 AC: 30825 AN: 60316

GnomAD4 genome AF: 0.502 AC: 76338 AN: 151934 Hom.: 19436 Cov.: 31 AF XY: 0.503 AC XY: 37344 AN XY: 74246

African (AFR) AF: 0.521 AC: 21560 AN: 41408

American (AMR) AF: 0.563 AC: 8591 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1974 AN: 3468

East Asian (EAS) AF: 0.744 AC: 3847 AN: 5168

South Asian (SAS) AF: 0.557 AC: 2686 AN: 4824

European-Finnish (FIN) AF: 0.396 AC: 4171 AN: 10530

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31922 AN: 67950

Other (OTH) AF: 0.516 AC: 1087 AN: 2108

Alfa AF: 0.487 Hom.: 30389

Bravo AF: 0.514

Asia WGS AF: 0.644 AC: 2236 AN: 3478

EpiCase AF: 0.470

EpiControl AF: 0.473

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.5
DANN	Benign	0.55
PhyloP100		-0.19
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: rs4871; hg19: chr6-26545632; COSMIC: COSV66433016;