5-83664915-A-G

Variant names:

• chr5-83664915-A-G
• rs3846635
• NM_001884.4:c.100+8509T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001884.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAPLN1	NM_001884.4	MANE Select	c.100+8509T>C		intron	N/A	NP_001875.1	P10915

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAPLN1	ENST00000274341.9	TSL:1 MANE Select	c.100+8509T>C		intron	N/A	ENSP00000274341.4	P10915
	HAPLN1	ENST00000875523.1		c.100+8509T>C		intron	N/A	ENSP00000545582.1
	HAPLN1	ENST00000936313.1		c.100+8509T>C		intron	N/A	ENSP00000606372.1

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

African (AFR) AF: 0.200 AC: 8291 AN: 41516

American (AMR) AF: 0.156 AC: 2379 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0674 AC: 234 AN: 3470

East Asian (EAS) AF: 0.166 AC: 862 AN: 5178

South Asian (SAS) AF: 0.0404 AC: 195 AN: 4824

European-Finnish (FIN) AF: 0.0675 AC: 715 AN: 10588

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0702 AC: 4776 AN: 68004

Other (OTH) AF: 0.114 AC: 240 AN: 2112

Alfa AF: 0.0861 Hom.: 2173

Bravo AF: 0.130

Asia WGS AF: 0.0960 AC: 334 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Benign	0.92
PhyloP100		0.84
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3846635; hg19: chr5-82960734;