Variant chr1-220880157-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6BP7

The ENST00000366903.8(HLX):c.300G>A(p.Ala100=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,612,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

HLX
ENST00000366903.8 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.72

Variant links:

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]

HLX links:

HLX-AS1 (HGNC:42509): (HLX antisense RNA 1)

HLX-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 1-220880157-G-A is Benign according to our data. Variant chr1-220880157-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3352307.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=2.72 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLX	NM_021958.4 linkuse as main transcript	c.300G>A	p.Ala100=	synonymous_variant	1/4	ENST00000366903.8	NP_068777.1
HLX-AS1	NR_046901.1 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
HLX	ENST00000366903.8 linkuse as main transcript	c.300G>A	p.Ala100=	synonymous_variant	1/4	1	NM_021958.4	ENSP00000355870	P1
HLX	ENST00000549319.2 linkuse as main transcript	n.727G>A		non_coding_transcript_exon_variant	1/1
HLX-AS1	ENST00000552026.1 linkuse as main transcript			upstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000414

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000211

AC:

AN:

241768

Hom.:

AF XY:

0.000174

AC XY:

AN XY:

132222

show subpopulations

Gnomad AFR exome

AF:

0.0000683

Gnomad AMR exome

AF:

0.000583

Gnomad ASJ exome

AF:

0.00212

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000656

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000370

Gnomad OTH exome

AF:

0.000505

GnomAD4 exome

AF:

0.000103

AC:

151

AN:

1460074

Hom.:

Cov.:

AF XY:

0.000103

AC XY:

AN XY:

726372

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000739

Gnomad4 ASJ exome

AF:

0.00238

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.000382

GnomAD4 genome

AF:

0.000414

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000315

Hom.:

Bravo

AF:

0.000782

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HLX-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 11, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.94

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over