rs3738182

Variant names:

• chr1-220884320-G-A
• rs3738182
• NM_021958.4:c.1083G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-220884320-G-A
• chr1-220884320-G-T

Variant summary

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

The NM_021958.4(HLX):​c.1083G>A​(p.Glu361Glu) 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
• Publications: 18 publications found

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]

ENSG00000286231 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021958.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLX	NM_021958.4	MANE Select	c.1083G>A	p.Glu361Glu	synonymous	Exon 4 of 4	NP_068777.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLX	ENST00000366903.8	TSL:1 MANE Select	c.1083G>A	p.Glu361Glu	synonymous	Exon 4 of 4	ENSP00000355870.5
	ENSG00000286231	ENST00000651706.1		n.*391G>A		non_coding_transcript_exon	Exon 9 of 9	ENSP00000499157.1
	ENSG00000286231	ENST00000651706.1		n.*391G>A		3_prime_UTR	Exon 9 of 9	ENSP00000499157.1

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

GnomAD2 exomes AF: 0.183 AC: 45529 AN: 249050 AF XY: 0.183

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 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

African (AFR) AF: 0.233 AC: 7797 AN: 33476

American (AMR) AF: 0.159 AC: 7106 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 6055 AN: 26112

East Asian (EAS) AF: 0.106 AC: 4191 AN: 39696

South Asian (SAS) AF: 0.189 AC: 16337 AN: 86230

European-Finnish (FIN) AF: 0.240 AC: 12813 AN: 53282

Middle Eastern (MID) AF: 0.164 AC: 945 AN: 5762

European-Non Finnish (NFE) AF: 0.192 AC: 213356 AN: 1111542

Other (OTH) AF: 0.185 AC: 11167 AN: 60342

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

African (AFR) AF: 0.240 AC: 9950 AN: 41458

American (AMR) AF: 0.168 AC: 2566 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 797 AN: 3470

East Asian (EAS) AF: 0.0891 AC: 459 AN: 5154

South Asian (SAS) AF: 0.190 AC: 917 AN: 4820

European-Finnish (FIN) AF: 0.256 AC: 2696 AN: 10530

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.187 AC: 12699 AN: 67940

Other (OTH) AF: 0.176 AC: 372 AN: 2116

Alfa AF: 0.189 Hom.: 8489

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.83
PhyloP100		0.37
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: rs3738182; hg19: chr1-221057662; COSMIC: COSV65044262; COSMIC: COSV65044262;