chr5-83665051-T-C

Variant names:

• chr5-83665051-T-C
• rs179851
• NM_001884.4:c.100+8373A>G

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+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
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 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+8373A>G		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+8373A>G		intron	N/A	ENSP00000274341.4	P10915
	HAPLN1	ENST00000875523.1		c.100+8373A>G		intron	N/A	ENSP00000545582.1
	HAPLN1	ENST00000936313.1		c.100+8373A>G		intron	N/A	ENSP00000606372.1

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

African (AFR) AF: 0.311 AC: 12849 AN: 41330

American (AMR) AF: 0.392 AC: 5984 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1177 AN: 3470

East Asian (EAS) AF: 0.542 AC: 2804 AN: 5172

South Asian (SAS) AF: 0.419 AC: 2016 AN: 4814

European-Finnish (FIN) AF: 0.341 AC: 3601 AN: 10552

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23136 AN: 67942

Other (OTH) AF: 0.368 AC: 776 AN: 2110

Alfa AF: 0.336 Hom.: 8600

Bravo AF: 0.353

Asia WGS AF: 0.520 AC: 1795 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.66
PhyloP100		0.18
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: rs179851; hg19: chr5-82960870;