Variant 1-220884186-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_021958.4(HLX):c.958-9G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00431 in 1,613,810 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 17 hom. )

Consequence

HLX
NM_021958.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.008342

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.860

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 1-220884186-G-A is Benign according to our data. Variant chr1-220884186-G-A is described in ClinVar as [Benign]. Clinvar id is 777942.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLX	NM_021958.4 linkuse as main transcript	c.958-9G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000366903.8

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
HLX	ENST00000366903.8 linkuse as main transcript	c.958-9G>A	splice_polypyrimidine_tract_variant, intron_variant		1	NM_021958.4	P1
HLX	ENST00000427693.1 linkuse as main transcript	c.157-9G>A	splice_polypyrimidine_tract_variant, intron_variant		3
HLX	ENST00000549319.2 linkuse as main transcript	n.4756G>A	non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.00364

AC:

554

AN:

152026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00753

Gnomad ASJ

AF:

0.00836

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00255

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00481

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00332

AC:

825

AN:

248768

Hom.:

AF XY:

0.00322

AC XY:

433

AN XY:

134578

show subpopulations

Gnomad AFR exome

AF:

0.00106

Gnomad AMR exome

AF:

0.00307

Gnomad ASJ exome

AF:

0.0113

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00435

Gnomad NFE exome

AF:

0.00411

Gnomad OTH exome

AF:

0.00512

GnomAD4 exome

AF:

0.00438

AC:

6402

AN:

1461666

Hom.:

Cov.:

AF XY:

0.00419

AC XY:

3047

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00342

Gnomad4 ASJ exome

AF:

0.0119

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.00330

Gnomad4 NFE exome

AF:

0.00484

Gnomad4 OTH exome

AF:

0.00530

GnomAD4 genome

AF:

0.00364

AC:

554

AN:

152144

Hom.:

Cov.:

AF XY:

0.00345

AC XY:

257

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.00752

Gnomad4 ASJ

AF:

0.00836

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00255

Gnomad4 NFE

AF:

0.00481

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00418

Hom.:

Bravo

AF:

0.00416

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00502

EpiControl

AF:

0.00557

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0083

dbscSNV1_RF

Benign

0.10

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