Variant 1-220881305-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_021958.4(HLX):c.704C>T(p.Ala235Val) variant causes a missense change. The variant allele was found at a frequency of 0.00288 in 1,613,996 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 10 hom., cov: 34)

Exomes 𝑓: 0.0030 ( 135 hom. )

Consequence

HLX
NM_021958.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.83

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004606515).

BP6

Variant 1-220881305-C-T is Benign according to our data. Variant chr1-220881305-C-T is described in ClinVar as [Benign]. Clinvar id is 779861.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00184 (281/152356) while in subpopulation SAS AF= 0.0439 (212/4832). AF 95% confidence interval is 0.039. There are 10 homozygotes in gnomad4. There are 191 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLX	NM_021958.4 linkuse as main transcript	c.704C>T	p.Ala235Val	missense_variant	2/4	ENST00000366903.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
HLX	ENST00000366903.8 linkuse as main transcript	c.704C>T	p.Ala235Val	missense_variant	2/4	1	NM_021958.4	P1
HLX	ENST00000427693.1 linkuse as main transcript	c.-98C>T		5_prime_UTR_variant	2/4	3
HLX	ENST00000549319.2 linkuse as main transcript	n.1875C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.00187

AC:

284

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0445

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00627

AC:

1577

AN:

251488

Hom.:

AF XY:

0.00808

AC XY:

1098

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00442

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000707

Gnomad SAS exome

AF:

0.0449

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000791

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.00299

AC:

4367

AN:

1461640

Hom.:

135

Cov.:

AF XY:

0.00422

AC XY:

3070

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00487

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.0444

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000369

Gnomad4 OTH exome

AF:

0.00378

GnomAD4 genome

AF:

0.00184

AC:

281

AN:

152356

Hom.:

Cov.:

AF XY:

0.00256

AC XY:

191

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00274

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000964

Gnomad4 SAS

AF:

0.0439

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000163

Hom.:

Bravo

AF:

0.000835

ExAC

AF:

0.00670

AC:

814

Asia WGS

AF:

0.0210

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.17

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Benign

-0.0089

Eigen_PC

Benign

0.21

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.80

MetaRNN

Benign

0.0046

MetaSVM

Uncertain

-0.22

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.31

Sift

Uncertain

0.012

Sift4G

Benign

0.23

Polyphen

0.18

Vest4

0.30

MVP

0.68

MPC

0.57

ClinPred

0.026

GERP RS

4.9

Varity_R

0.19

gMVP

0.58

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