Variant rs2070180 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005335.6(HCLS1):c.1081G>A(p.Glu361Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 1,613,780 control chromosomes in the GnomAD database, including 59,047 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.22 ( 4219 hom., cov: 31)

Exomes 𝑓: 0.27 ( 54828 hom. )

Consequence

HCLS1
NM_005335.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.04

Variant links:

Genes affected

HCLS1 (HGNC:4844): (hematopoietic cell-specific Lyn substrate 1) Enables RNA polymerase II-specific DNA-binding transcription factor binding activity and protein kinase binding activity. Involved in several processes, including positive regulation of intracellular signal transduction; positive regulation of protein phosphorylation; and regulation of transcription, DNA-templated. Located in cytosol; nucleus; and plasma membrane. Part of transcription regulator complex. [provided by Alliance of Genome Resources, Apr 2022]

HCLS1 links:

HCLS1 (HGNC:):

HCLS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053710043).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCLS1	NM_005335.6 linkuse as main transcript	c.1081G>A	p.Glu361Lys	missense_variant	12/14	ENST00000314583.8	NP_005326.3	P14317-1
HCLS1	NM_001292041.2 linkuse as main transcript	c.970G>A	p.Glu324Lys	missense_variant	11/13		NP_001278970.2	P14317

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HCLS1	ENST00000314583.8 linkuse as main transcript	c.1081G>A	p.Glu361Lys	missense_variant	12/14	1	NM_005335.6	ENSP00000320176.3		P14317-1

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33393

AN:

151928

Hom.:

4220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.397

Gnomad AMR

AF:

0.145

Gnomad ASJ

AF:

0.200

Gnomad EAS

AF:

0.0828

Gnomad SAS

AF:

0.0981

Gnomad FIN

AF:

0.312

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.286

Gnomad OTH

AF:

0.211

GnomAD3 exomes

AF:

0.213

AC:

53017

AN:

248910

Hom.:

6717

AF XY:

0.212

AC XY:

28589

AN XY:

134752

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.196

Gnomad EAS exome

AF:

0.0789

Gnomad SAS exome

AF:

0.106

Gnomad FIN exome

AF:

0.316

Gnomad NFE exome

AF:

0.285

Gnomad OTH exome

AF:

0.219

GnomAD4 exome

AF:

0.265

AC:

387460

AN:

1461732

Hom.:

54828

Cov.:

AF XY:

0.260

AC XY:

189054

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.141

Gnomad4 AMR exome

AF:

0.123

Gnomad4 ASJ exome

AF:

0.197

Gnomad4 EAS exome

AF:

0.0884

Gnomad4 SAS exome

AF:

0.109

Gnomad4 FIN exome

AF:

0.310

Gnomad4 NFE exome

AF:

0.295

Gnomad4 OTH exome

AF:

0.236

GnomAD4 genome

AF:

0.220

AC:

33386

AN:

152048

Hom.:

4219

Cov.:

AF XY:

0.214

AC XY:

15872

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.145

Gnomad4 AMR

AF:

0.144

Gnomad4 ASJ

AF:

0.200

Gnomad4 EAS

AF:

0.0829

Gnomad4 SAS

AF:

0.0981

Gnomad4 FIN

AF:

0.312

Gnomad4 NFE

AF:

0.286

Gnomad4 OTH

AF:

0.209

Alfa

AF:

0.260

Hom.:

13175

Bravo

AF:

0.209

TwinsUK

AF:

0.293

AC:

1085

ALSPAC

AF:

0.297

AC:

1146

ESP6500AA

AF:

0.150

AC:

662

ESP6500EA

AF:

0.287

AC:

2464

ExAC

AF:

0.216

AC:

26253

Asia WGS

AF:

0.110

AC:

386

AN:

3478

EpiCase

AF:

0.272

EpiControl

AF:

0.266

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.36

T;T

Eigen

Benign

0.084

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.57

T;T

MetaRNN

Benign

0.0054

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.071

Sift

Benign

0.071

T;T

Sift4G

Benign

0.32

T;T

Polyphen

0.93

P;P

Vest4

0.18

MPC

0.23

ClinPred

0.019

GERP RS

4.1

Varity_R

0.12

gMVP

0.37

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over