5-83665051-T-C

Position:

• chr5-83665051-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.100+8373A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 151,858 control chromosomes in the GnomAD database, including 9,389 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 0.35 (9389 hom., cov: 32)
• Consequence: HAPLN1 NM_001884.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAPLN1	NM_001884.4	c.100+8373A>G		intron_variant		ENST00000274341.9	NP_001875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAPLN1	ENST00000274341.9	c.100+8373A>G		intron_variant		1	NM_001884.4	ENSP00000274341.4

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52816 AN: 151742 Hom.: 9384 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.348 AC: 52848 AN: 151858 Hom.: 9389 Cov.: 32 AF XY: 0.350 AC XY: 25952 AN XY: 74222

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.368

Alfa AF: 0.330 Hom.: 5755

Bravo AF: 0.353

Asia WGS AF: 0.520 AC: 1795 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.66

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: rs179851; hg19: chr5-82960870;