Variant rs2073420 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001352514.2(HLCS):c.2122-30G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,394,790 control chromosomes in the GnomAD database, including 147,121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13405 hom., cov: 32)

Exomes 𝑓: 0.46 ( 133716 hom. )

Consequence

HLCS
NM_001352514.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.115

Variant links:

Genes affected

HLCS (HGNC:4976): (holocarboxylase synthetase) This gene encodes an enzyme that catalyzes the binding of biotin to carboxylases and histones. The protein plays an important role in gluconeogenesis, fatty acid synthesis and branched chain amino acid catabolism. Defects in this gene are the cause of holocarboxylase synthetase deficiency. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Jun 2011]

HLCS links:

HLCS (HGNC:):

HLCS links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 21-36759871-C-T is Benign according to our data. Variant chr21-36759871-C-T is described in ClinVar as [Benign]. Clinvar id is 256035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLCS	NM_001352514.2 linkuse as main transcript	c.2122-30G>A		intron_variant		ENST00000674895.3	NP_001339443.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLCS	ENST00000674895.3 linkuse as main transcript	c.2122-30G>A		intron_variant			NM_001352514.2	ENSP00000502087.2		P50747-2A0A8C8QSB1

Frequencies

GnomAD3 genomes

AF:

0.414

AC:

62817

AN:

151836

Hom.:

13404

Cov.:

show subpopulations

Gnomad AFR

AF:

0.326

Gnomad AMI

AF:

0.545

Gnomad AMR

AF:

0.376

Gnomad ASJ

AF:

0.449

Gnomad EAS

AF:

0.308

Gnomad SAS

AF:

0.548

Gnomad FIN

AF:

0.393

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.473

Gnomad OTH

AF:

0.433

GnomAD3 exomes

AF:

0.431

AC:

108284

AN:

251052

Hom.:

24149

AF XY:

0.444

AC XY:

60350

AN XY:

135794

show subpopulations

Gnomad AFR exome

AF:

0.319

Gnomad AMR exome

AF:

0.326

Gnomad ASJ exome

AF:

0.438

Gnomad EAS exome

AF:

0.339

Gnomad SAS exome

AF:

0.548

Gnomad FIN exome

AF:

0.389

Gnomad NFE exome

AF:

0.470

Gnomad OTH exome

AF:

0.438

GnomAD4 exome

AF:

0.460

AC:

572297

AN:

1242836

Hom.:

133716

Cov.:

AF XY:

0.466

AC XY:

293232

AN XY:

629918

show subpopulations

Gnomad4 AFR exome

AF:

0.315

Gnomad4 AMR exome

AF:

0.331

Gnomad4 ASJ exome

AF:

0.442

Gnomad4 EAS exome

AF:

0.302

Gnomad4 SAS exome

AF:

0.548

Gnomad4 FIN exome

AF:

0.385

Gnomad4 NFE exome

AF:

0.476

Gnomad4 OTH exome

AF:

0.448

GnomAD4 genome

AF:

0.413

AC:

62821

AN:

151954

Hom.:

13405

Cov.:

AF XY:

0.412

AC XY:

30567

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.326

Gnomad4 AMR

AF:

0.375

Gnomad4 ASJ

AF:

0.449

Gnomad4 EAS

AF:

0.307

Gnomad4 SAS

AF:

0.546

Gnomad4 FIN

AF:

0.393

Gnomad4 NFE

AF:

0.473

Gnomad4 OTH

AF:

0.430

Alfa

AF:

0.374

Hom.:

2047

Bravo

AF:

0.407

Asia WGS

AF:

0.411

AC:

1429

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Holocarboxylase synthetase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.1

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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