rs3787764

Positions:

• chr21-36859938-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+36922C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,090 control chromosomes in the GnomAD database, including 6,284 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 0.27 (6284 hom., cov: 32)
• Consequence: HLCS NM_001352514.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLCS	NM_001352514.2	c.1892+36922C>T		intron_variant		ENST00000674895.3	NP_001339443.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLCS	ENST00000674895.3	c.1892+36922C>T		intron_variant			NM_001352514.2	ENSP00000502087.2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40528 AN: 151972 Hom.: 6269 Cov.: 32

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.0209

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.267 AC: 40574 AN: 152090 Hom.: 6284 Cov.: 32 AF XY: 0.267 AC XY: 19834 AN XY: 74362

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.258

Alfa AF: 0.256 Hom.: 958

Bravo AF: 0.266

Asia WGS AF: 0.285 AC: 988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.75

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

Other links and lift over

dbSNP: rs3787764; hg19: chr21-38232238;