5-83720924-C-T

Variant names:

• chr5-83720924-C-T
• rs3734092
• NM_001884.4:c.-162G>A

Variant summary

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

The NM_001884.4(HAPLN1):​c.-162G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 150,598 control chromosomes in the GnomAD database, including 41,778 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 0.75 (41746 hom., cov: 30)
  • Exomes 𝑓: 0.71 (32 hom.)
• Consequence: HAPLN1 NM_001884.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.671

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAPLN1	NM_001884.4	c.-162G>A		upstream_gene_variant		ENST00000274341.9	NP_001875.1
HAPLN1	XM_017009051.2	c.-212G>A		upstream_gene_variant			XP_016864540.1
HAPLN1	XM_017009053.2	c.-162G>A		upstream_gene_variant			XP_016864542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAPLN1	ENST00000274341.9	c.-162G>A		upstream_gene_variant		1	NM_001884.4	ENSP00000274341.4
HAPLN1	ENST00000515590.1	c.-212G>A		upstream_gene_variant		5		ENSP00000423836.1

Frequencies

GnomAD3 genomes AF: 0.746 AC: 112113 AN: 150366 Hom.: 41704 Cov.: 30

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.756

GnomAD4 exome AF: 0.710 AC: 88 AN: 124 Hom.: 32 Cov.: 0 AF XY: 0.744 AC XY: 67 AN XY: 90

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.400

Gnomad4 NFE exome AF: 0.729

Gnomad4 OTH exome AF: 0.833

GnomAD4 genome AF: 0.746 AC: 112208 AN: 150474 Hom.: 41746 Cov.: 30 AF XY: 0.738 AC XY: 54259 AN XY: 73514

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.739

Gnomad4 ASJ AF: 0.728

Gnomad4 EAS AF: 0.815

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.660

Gnomad4 NFE AF: 0.757

Gnomad4 OTH AF: 0.760

Alfa AF: 0.753 Hom.: 3877

Bravo AF: 0.755

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.69

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: rs3734092; hg19: chr5-83016743;