Variant chr3-121632468-G-GGGCTCAGGCTCA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_005335.6(HCLS1):c.1103_1104insTGAGCCTGAGCC(p.Pro372_Glu375dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,612,982 control chromosomes in the GnomAD database, including 45,549 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3974 hom., cov: 25)

Exomes 𝑓: 0.23 ( 41575 hom. )

Consequence

HCLS1
NM_005335.6 inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0890

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 made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 3-121632468-G-GGGCTCAGGCTCA is Benign according to our data. Variant chr3-121632468-G-GGGCTCAGGCTCA is described in ClinVar as [Benign]. Clinvar id is 1291285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HCLS1	NM_005335.6 linkuse as main transcript	c.1103_1104insTGAGCCTGAGCC	p.Pro372_Glu375dup	inframe_insertion	12/14	ENST00000314583.8
HCLS1	NM_001292041.2 linkuse as main transcript	c.992_993insTGAGCCTGAGCC	p.Pro335_Glu338dup	inframe_insertion	11/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCLS1	ENST00000314583.8 linkuse as main transcript	c.1103_1104insTGAGCCTGAGCC	p.Pro372_Glu375dup	inframe_insertion	12/14	1	NM_005335.6	P1	P14317-1
HCLS1	ENST00000428394.6 linkuse as main transcript	c.992_993insTGAGCCTGAGCC	p.Pro335_Glu338dup	inframe_insertion	11/13	2
HCLS1	ENST00000473883.5 linkuse as main transcript	n.1906_1907insTGAGCCTGAGCC		non_coding_transcript_exon_variant	7/9	2
HCLS1	ENST00000495491.5 linkuse as main transcript	c.418_419insTGAGCCTGAGCC		3_prime_UTR_variant, NMD_transcript_variant	11/11	2			P14317-2

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33125

AN:

151376

Hom.:

3976

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.242

Gnomad AMR

AF:

0.202

Gnomad ASJ

AF:

0.303

Gnomad EAS

AF:

0.446

Gnomad SAS

AF:

0.214

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.244

Gnomad OTH

AF:

0.253

GnomAD4 exome

AF:

0.234

AC:

341474

AN:

1461488

Hom.:

41575

Cov.:

AF XY:

0.234

AC XY:

170396

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.142

Gnomad4 AMR exome

AF:

0.150

Gnomad4 ASJ exome

AF:

0.301

Gnomad4 EAS exome

AF:

0.399

Gnomad4 SAS exome

AF:

0.228

Gnomad4 FIN exome

AF:

0.212

Gnomad4 NFE exome

AF:

0.232

Gnomad4 OTH exome

AF:

0.256

GnomAD4 genome

AF:

0.219

AC:

33122

AN:

151494

Hom.:

3974

Cov.:

AF XY:

0.216

AC XY:

16012

AN XY:

73990

show subpopulations

Gnomad4 AFR

AF:

0.148

Gnomad4 AMR

AF:

0.201

Gnomad4 ASJ

AF:

0.303

Gnomad4 EAS

AF:

0.446

Gnomad4 SAS

AF:

0.213

Gnomad4 FIN

AF:

0.211

Gnomad4 NFE

AF:

0.244

Gnomad4 OTH

AF:

0.250

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2019	This variant is associated with the following publications: (PMID: 15022330) -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 12, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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