rs3738182

Positions:

• chr1-220884320-G-A

Variant summary

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

The NM_021958.4(HLX):​c.1083G>A​(p.Glu361=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,613,072 control chromosomes in the GnomAD database, including 30,795 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 0.20 (3247 hom., cov: 32)
  • Exomes 𝑓: 0.19 (27548 hom.)
• Consequence: HLX NM_021958.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.372

Genes affected

HLX (HGNC:4978): (H2.0 like homeobox) Enables sequence-specific DNA binding activity. Predicted to be involved in cell differentiation and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including animal organ development; enteric nervous system development; and regulation of T-helper cell differentiation. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=0.372 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLX	NM_021958.4	c.1083G>A	p.Glu361=	synonymous_variant	4/4	ENST00000366903.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLX	ENST00000366903.8	c.1083G>A	p.Glu361=	synonymous_variant	4/4	1	NM_021958.4	P1
HLX	ENST00000427693.1	c.282G>A	p.Glu94=	synonymous_variant	4/4	3
HLX	ENST00000549319.2	n.4890G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30733 AN: 151858 Hom.: 3244 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.0894

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.176

GnomAD3 exomes AF: 0.183 AC: 45529 AN: 249050 Hom.: 4392 AF XY: 0.183 AC XY: 24722 AN XY: 134928

Gnomad AFR exome AF: 0.238

Gnomad AMR exome AF: 0.156

Gnomad ASJ exome AF: 0.229

Gnomad EAS exome AF: 0.0572

Gnomad SAS exome AF: 0.189

Gnomad FIN exome AF: 0.247

Gnomad NFE exome AF: 0.186

Gnomad OTH exome AF: 0.172

GnomAD4 exome AF: 0.191 AC: 279767 AN: 1461096 Hom.: 27548 Cov.: 41 AF XY: 0.191 AC XY: 138834 AN XY: 726802

Gnomad4 AFR exome AF: 0.233

Gnomad4 AMR exome AF: 0.159

Gnomad4 ASJ exome AF: 0.232

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.189

Gnomad4 FIN exome AF: 0.240

Gnomad4 NFE exome AF: 0.192

Gnomad4 OTH exome AF: 0.185

GnomAD4 genome AF: 0.202 AC: 30749 AN: 151976 Hom.: 3247 Cov.: 32 AF XY: 0.201 AC XY: 14941 AN XY: 74274

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.0891

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.176

Alfa AF: 0.187 Hom.: 5329

Bravo AF: 0.195

Asia WGS AF: 0.159 AC: 554 AN: 3476

EpiCase AF: 0.180

EpiControl AF: 0.180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.83

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: rs3738182; hg19: chr1-221057662; COSMIC: COSV65044262; COSMIC: COSV65044262;