rs11701035

chr21-36868670-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001352514.2(HLCS):c.1892+28190C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 151,696 control chromosomes in the GnomAD database, including 3,084 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 0.20 (3084 hom., cov: 31)
• Consequence: HLCS NM_001352514.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLCS	NM_001352514.2	c.1892+28190C>T		intron_variant		ENST00000674895.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLCS	ENST00000674895.3	c.1892+28190C>T		intron_variant			NM_001352514.2	P4

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29641 AN: 151580 Hom.: 3078 Cov.: 31

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.0819

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.220

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.196 AC: 29669 AN: 151696 Hom.: 3084 Cov.: 31 AF XY: 0.191 AC XY: 14189 AN XY: 74120

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.0819

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.220

Alfa AF: 0.189 Hom.: 2790

Bravo AF: 0.204

Asia WGS AF: 0.166 AC: 582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.6
Dann	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs11701035; hg19: chr21-38240970;