chr5-83689920-T-G

Variant names:

• chr5-83689920-T-G
• rs4466137
• NM_001884.4:c.-26-16371A>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.-26-16371A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 152,008 control chromosomes in the GnomAD database, including 44,944 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 0.77 (44944 hom., cov: 32)
• Consequence: HAPLN1 NM_001884.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.906
• Publications: 33 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 = 0.809 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.-26-16371A>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.-26-16371A>C		intron	N/A	ENSP00000274341.4	P10915
	HAPLN1	ENST00000875523.1		c.-27+3250A>C		intron	N/A	ENSP00000545582.1
	HAPLN1	ENST00000936313.1		c.-26-16371A>C		intron	N/A	ENSP00000606372.1

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116550 AN: 151890 Hom.: 44890 Cov.: 32

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.767 AC: 116665 AN: 152008 Hom.: 44944 Cov.: 32 AF XY: 0.761 AC XY: 56562 AN XY: 74294

African (AFR) AF: 0.813 AC: 33745 AN: 41502

American (AMR) AF: 0.749 AC: 11434 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2525 AN: 3464

East Asian (EAS) AF: 0.829 AC: 4284 AN: 5166

South Asian (SAS) AF: 0.622 AC: 2995 AN: 4818

European-Finnish (FIN) AF: 0.700 AC: 7391 AN: 10552

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.762 AC: 51735 AN: 67920

Other (OTH) AF: 0.777 AC: 1640 AN: 2110

Alfa AF: 0.765 Hom.: 133549

Bravo AF: 0.778

Asia WGS AF: 0.744 AC: 2585 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.54
DANN	Benign	0.74
PhyloP100		-0.91
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: rs4466137; hg19: chr5-82985739;