Genetic Variant HAPLN1:c.-27+2550G>A (chr5-83720924-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000936313.1(HAPLN1):c.-27+2550G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 150,598 control chromosomes in the GnomAD database, including 41,778 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 0.75 ( 41746 hom., cov: 30)

Exomes 𝑓: 0.71 ( 32 hom. )

Consequence

HAPLN1
ENST00000936313.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.671

Publications

5 publications found

Variant links:

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]

HAPLN1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000936313.1. 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.-162G>A		upstream_gene	N/A	NP_001875.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HAPLN1	ENST00000936313.1		c.-27+2550G>A	intron	N/A	ENSP00000606372.1
HAPLN1	ENST00000274341.9	TSL:1 MANE Select	c.-162G>A	upstream_gene	N/A	ENSP00000274341.4
HAPLN1	ENST00000875523.1		c.-252G>A	upstream_gene	N/A	ENSP00000545582.1

Frequencies

GnomAD3 genomes

AF:

0.746

AC:

112113

AN:

150366

Hom.:

41704

Cov.:

show subpopulations

Gnomad AFR

AF:

0.759

Gnomad AMI

AF:

0.795

Gnomad AMR

AF:

0.739

Gnomad ASJ

AF:

0.728

Gnomad EAS

AF:

0.815

Gnomad SAS

AF:

0.607

Gnomad FIN

AF:

0.660

Gnomad MID

AF:

0.661

Gnomad NFE

AF:

0.757

Gnomad OTH

AF:

0.756

GnomAD4 exome

AF:

0.710

AC:

AN:

124

Hom.:

Cov.:

AF XY:

0.744

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.400

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.729

AC:

AN:

Other (OTH)

AF:

0.833

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.746

AC:

112208

AN:

150474

Hom.:

41746

Cov.:

AF XY:

0.738

AC XY:

54259

AN XY:

73514

show subpopulations

African (AFR)

AF:

0.760

AC:

31095

AN:

40934

American (AMR)

AF:

0.739

AC:

11185

AN:

15144

Ashkenazi Jewish (ASJ)

AF:

0.728

AC:

2510

AN:

3450

East Asian (EAS)

AF:

0.815

AC:

4173

AN:

5120

South Asian (SAS)

AF:

0.607

AC:

2898

AN:

4778

European-Finnish (FIN)

AF:

0.660

AC:

6811

AN:

10322

Middle Eastern (MID)

AF:

0.653

AC:

192

AN:

294

European-Non Finnish (NFE)

AF:

0.757

AC:

51036

AN:

67438

Other (OTH)

AF:

0.760

AC:

1589

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1424

2848

4272

5696

7120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

838

1676

2514

3352

4190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.754

Hom.:

9736

Bravo

AF:

0.755

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.4

(source)

DANN

Benign

0.69

PhyloP100

-0.67

PromoterAI

-0.065

Neutral

(source)

Mutation Taster

=298/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over