rs4871

Positions:

• chr6-26545404-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000377575.3(HMGN4):​c.198G>A​(p.Gly66=) 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 ENST00000377575.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
HMGN4	NM_006353.3	c.198G>A	p.Gly66=	synonymous_variant	2/2	ENST00000377575.3	NP_006344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMGN4	ENST00000377575.3	c.198G>A	p.Gly66=	synonymous_variant	2/2	1	NM_006353.3	ENSP00000366798	P1
	ENST00000707189.1	n.1000-7783G>A		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes AF: 0.516 AC: 129030 AN: 250300 Hom.: 34475 AF XY: 0.510 AC XY: 68989 AN XY: 135326

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 SAS exome AF: 0.535

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

Gnomad4 AFR exome AF: 0.510

Gnomad4 AMR exome AF: 0.586

Gnomad4 ASJ exome AF: 0.559

Gnomad4 EAS exome AF: 0.734

Gnomad4 SAS exome AF: 0.529

Gnomad4 FIN exome AF: 0.411

Gnomad4 NFE exome AF: 0.470

Gnomad4 OTH exome AF: 0.511

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

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.744

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.516

Alfa AF: 0.479 Hom.: 21767

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

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: rs4871; hg19: chr6-26545632; COSMIC: COSV66433016;