dbSNP rs1128163: HCLS1:c.*120T>C (chr3-121631726-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005335.6(HCLS1):c.*120T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,053,022 control chromosomes in the GnomAD database, including 31,156 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 0.23 ( 4169 hom., cov: 31)

Exomes 𝑓: 0.24 ( 26987 hom. )

Consequence

HCLS1
NM_005335.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05

Publications

10 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCLS1	NM_005335.6 link	c.*120T>C		3_prime_UTR_variant	Exon 14 of 14	ENST00000314583.8	NP_005326.3	P14317-1
HCLS1	NM_001292041.2 link	c.*120T>C		3_prime_UTR_variant	Exon 13 of 13		NP_001278970.2	P14317

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HCLS1	ENST00000314583.8 link	c.*120T>C	3_prime_UTR_variant	Exon 14 of 14	1	NM_005335.6	ENSP00000320176.3	P14317-1
HCLS1	ENST00000473883.5 link	n.2384T>C	non_coding_transcript_exon_variant	Exon 9 of 9	2
HCLS1	ENST00000428394.6 link	c.*120T>C	3_prime_UTR_variant	Exon 13 of 13	2		ENSP00000387645.2	E7EVW7

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34303

AN:

151862

Hom.:

4173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.242

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.303

Gnomad EAS

AF:

0.447

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.315

Gnomad NFE

AF:

0.245

Gnomad OTH

AF:

0.260

GnomAD4 exome

AF:

0.239

AC:

215004

AN:

901042

Hom.:

26987

Cov.:

AF XY:

0.239

AC XY:

108818

AN XY:

455572

show subpopulations

African (AFR)

AF:

0.166

AC:

3587

AN:

21576

American (AMR)

AF:

0.163

AC:

4622

AN:

28392

Ashkenazi Jewish (ASJ)

AF:

0.303

AC:

5391

AN:

17794

East Asian (EAS)

AF:

0.394

AC:

13677

AN:

34682

South Asian (SAS)

AF:

0.231

AC:

13910

AN:

60154

European-Finnish (FIN)

AF:

0.213

AC:

9418

AN:

44204

Middle Eastern (MID)

AF:

0.334

AC:

1028

AN:

3076

European-Non Finnish (NFE)

AF:

0.235

AC:

152716

AN:

650274

Other (OTH)

AF:

0.261

AC:

10655

AN:

40890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

8094

16188

24283

32377

40471

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.226

AC:

34300

AN:

151980

Hom.:

4169

Cov.:

AF XY:

0.224

AC XY:

16609

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.170

AC:

7042

AN:

41448

American (AMR)

AF:

0.204

AC:

3116

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.303

AC:

1053

AN:

3470

East Asian (EAS)

AF:

0.447

AC:

2294

AN:

5132

South Asian (SAS)

AF:

0.216

AC:

1037

AN:

4806

European-Finnish (FIN)

AF:

0.211

AC:

2236

AN:

10574

Middle Eastern (MID)

AF:

0.305

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.245

AC:

16668

AN:

67958

Other (OTH)

AF:

0.258

AC:

545

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1352

2704

4055

5407

6759

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.233

Hom.:

2012

Bravo

AF:

0.225

Asia WGS

AF:

0.288

AC:

1000

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.0

(source)

DANN

Benign

0.63

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs1128163

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over