chr5-83664915-A-G

Position:

• chr5-83664915-A-G

Variant summary

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

The NM_001884.4(HAPLN1):​c.100+8509T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,176 control chromosomes in the GnomAD database, including 1,360 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 0.12 (1360 hom., cov: 32)
• Consequence: HAPLN1 NM_001884.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.844

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=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAPLN1	NM_001884.4	c.100+8509T>C		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+8509T>C		intron_variant		1	NM_001884.4	ENSP00000274341.4

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17679 AN: 152058 Hom.: 1349 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.0410

Gnomad FIN AF: 0.0675

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0702

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.117 AC: 17730 AN: 152176 Hom.: 1360 Cov.: 32 AF XY: 0.115 AC XY: 8565 AN XY: 74400

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.0674

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.0404

Gnomad4 FIN AF: 0.0675

Gnomad4 NFE AF: 0.0702

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0764 Hom.: 752

Bravo AF: 0.130

Asia WGS AF: 0.0960 AC: 334 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Benign	0.92

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: rs3846635; hg19: chr5-82960734;