Variant chr21-36767331-C-A 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.1893-46G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 1,580,300 control chromosomes in the GnomAD database, including 233,087 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 26905 hom., cov: 31)

Exomes 𝑓: 0.53 ( 206182 hom. )

Consequence

HLCS
NM_001352514.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.208

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=-0.9).

BP6

Variant 21-36767331-C-A is Benign according to our data. Variant chr21-36767331-C-A is described in ClinVar as [Benign]. Clinvar id is 256034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.689 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.1893-46G>T		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.1893-46G>T		intron_variant			NM_001352514.2	ENSP00000502087.2		P50747-2A0A8C8QSB1

Frequencies

GnomAD3 genomes

AF:

0.589

AC:

89404

AN:

151846

Hom.:

26847

Cov.:

show subpopulations

Gnomad AFR

AF:

0.696

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.619

Gnomad ASJ

AF:

0.550

Gnomad EAS

AF:

0.687

Gnomad SAS

AF:

0.470

Gnomad FIN

AF:

0.606

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.520

Gnomad OTH

AF:

0.572

GnomAD3 exomes

AF:

0.568

AC:

142613

AN:

251048

Hom.:

41302

AF XY:

0.555

AC XY:

75365

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.700

Gnomad AMR exome

AF:

0.674

Gnomad ASJ exome

AF:

0.560

Gnomad EAS exome

AF:

0.657

Gnomad SAS exome

AF:

0.467

Gnomad FIN exome

AF:

0.610

Gnomad NFE exome

AF:

0.523

Gnomad OTH exome

AF:

0.562

GnomAD4 exome

AF:

0.534

AC:

763109

AN:

1428336

Hom.:

206182

Cov.:

AF XY:

0.531

AC XY:

378170

AN XY:

712602

show subpopulations

Gnomad4 AFR exome

AF:

0.708

Gnomad4 AMR exome

AF:

0.669

Gnomad4 ASJ exome

AF:

0.557

Gnomad4 EAS exome

AF:

0.697

Gnomad4 SAS exome

AF:

0.467

Gnomad4 FIN exome

AF:

0.614

Gnomad4 NFE exome

AF:

0.517

Gnomad4 OTH exome

AF:

0.549

GnomAD4 genome

AF:

0.589

AC:

89519

AN:

151964

Hom.:

26905

Cov.:

AF XY:

0.592

AC XY:

43955

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.696

Gnomad4 AMR

AF:

0.619

Gnomad4 ASJ

AF:

0.550

Gnomad4 EAS

AF:

0.687

Gnomad4 SAS

AF:

0.472

Gnomad4 FIN

AF:

0.606

Gnomad4 NFE

AF:

0.520

Gnomad4 OTH

AF:

0.575

Alfa

AF:

0.565

Hom.:

4845

Bravo

AF:

0.596

Asia WGS

AF:

0.587

AC:

2041

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	Mar 03, 2015	- -

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

-0.90

CADD

Benign

0.49

DANN

Benign

0.53

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