rs336963

Positions:

• chr5-83673885-G-A
• chr5-83673885-G-C

Variant summary

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

The NM_001884.4(HAPLN1):​c.-26-336C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 215,010 control chromosomes in the GnomAD database, including 13,147 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 0.34 (9160 hom., cov: 33)
  • Exomes 𝑓: 0.34 (3987 hom.)
• Consequence: HAPLN1 NM_001884.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970

Genes affected

HAPLN1 (HGNC:2380): (hyaluronan and proteoglycan link protein 1) Predicted to enable hyaluronic acid binding activity. Predicted to be an extracellular matrix structural constituent conferring compression resistance. Predicted to be involved in central nervous system development and skeletal system development. Colocalizes with collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAPLN1	NM_001884.4	c.-26-336C>T		intron_variant		ENST00000274341.9	NP_001875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAPLN1	ENST00000274341.9	c.-26-336C>T		intron_variant		1	NM_001884.4	ENSP00000274341.4

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52157 AN: 152008 Hom.: 9155 Cov.: 33

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.356

GnomAD4 exome AF: 0.344 AC: 21634 AN: 62884 Hom.: 3987 AF XY: 0.350 AC XY: 11319 AN XY: 32338

Gnomad4 AFR exome AF: 0.291

Gnomad4 AMR exome AF: 0.409

Gnomad4 ASJ exome AF: 0.323

Gnomad4 EAS exome AF: 0.511

Gnomad4 SAS exome AF: 0.410

Gnomad4 FIN exome AF: 0.346

Gnomad4 NFE exome AF: 0.327

Gnomad4 OTH exome AF: 0.355

GnomAD4 genome AF: 0.343 AC: 52193 AN: 152126 Hom.: 9160 Cov.: 33 AF XY: 0.345 AC XY: 25641 AN XY: 74380

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.529

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.362

Alfa AF: 0.319 Hom.: 4157

Bravo AF: 0.348

Asia WGS AF: 0.507 AC: 1762 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.8
DANN	Benign	0.59

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: rs336963; hg19: chr5-82969704;