5-83690330-T-C

Variant summary

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

The NM_001884.4(HAPLN1):c.-26-16781A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 151,906 control chromosomes in the GnomAD database, including 25,921 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 0.57 (25921 hom., cov: 33)
• Consequence: HAPLN1 NM_001884.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150

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=-0.51).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAPLN1	NM_001884.4	c.-26-16781A>G		intron_variant		ENST00000274341.9
HAPLN1	XM_017009051.2	c.-76-14993A>G		intron_variant
HAPLN1	XM_017009052.2	c.-27+2840A>G		intron_variant
HAPLN1	XM_017009053.2	c.-26-16781A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAPLN1	ENST00000274341.9	c.-26-16781A>G		intron_variant		1	NM_001884.4	P1
HAPLN1	ENST00000515590.1	c.-76-14993A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85929 AN: 151788 Hom.: 25905 Cov.: 33

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.566 AC: 85986 AN: 151906 Hom.: 25921 Cov.: 33 AF XY: 0.564 AC XY: 41837 AN XY: 74244

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.636

Gnomad4 EAS AF: 0.538

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.651

Gnomad4 NFE AF: 0.676

Gnomad4 OTH AF: 0.618

Alfa AF: 0.650 Hom.: 57808

Bravo AF: 0.558

Asia WGS AF: 0.535 AC: 1859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	8.8
Dann	Benign	0.85

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: rs16898; hg19: chr5-82986149;