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GeneBe

5-83644550-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001884.4(HAPLN1):c.588C>T(p.Asp196=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 1,604,844 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0021 ( 5 hom. )

Consequence

HAPLN1
NM_001884.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.61
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-83644550-G-A is Benign according to our data. Variant chr5-83644550-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2655579.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.61 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 242 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HAPLN1NM_001884.4 linkuse as main transcriptc.588C>T p.Asp196= synonymous_variant 4/5 ENST00000274341.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HAPLN1ENST00000274341.9 linkuse as main transcriptc.588C>T p.Asp196= synonymous_variant 4/51 NM_001884.4 P1
HAPLN1ENST00000510978.5 linkuse as main transcriptc.588C>T p.Asp196= synonymous_variant 3/32
HAPLN1ENST00000508307.5 linkuse as main transcriptc.588C>T p.Asp196= synonymous_variant 4/43
HAPLN1ENST00000503117.1 linkuse as main transcript downstream_gene_variant 2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00159
AC:
242
AN:
152150
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000459
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00137
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00424
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00225
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.00170
AC:
411
AN:
241788
Hom.:
0
AF XY:
0.00160
AC XY:
210
AN XY:
130842
show subpopulations
Gnomad AFR exome
AF:
0.000192
Gnomad AMR exome
AF:
0.000405
Gnomad ASJ exome
AF:
0.00135
Gnomad EAS exome
AF:
0.0000570
Gnomad SAS exome
AF:
0.0000687
Gnomad FIN exome
AF:
0.00359
Gnomad NFE exome
AF:
0.00263
Gnomad OTH exome
AF:
0.00189
GnomAD4 exome
AF:
0.00205
AC:
2983
AN:
1452576
Hom.:
5
Cov.:
36
AF XY:
0.00201
AC XY:
1453
AN XY:
722246
show subpopulations
Gnomad4 AFR exome
AF:
0.000304
Gnomad4 AMR exome
AF:
0.000394
Gnomad4 ASJ exome
AF:
0.00140
Gnomad4 EAS exome
AF:
0.0000256
Gnomad4 SAS exome
AF:
0.0000589
Gnomad4 FIN exome
AF:
0.00340
Gnomad4 NFE exome
AF:
0.00238
Gnomad4 OTH exome
AF:
0.00157
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00159
AC:
242
AN:
152268
Hom.:
0
Cov.:
33
AF XY:
0.00165
AC XY:
123
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.000457
Gnomad4 AMR
AF:
0.00137
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00424
Gnomad4 NFE
AF:
0.00225
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00172
Hom.:
0
Bravo
AF:
0.00123
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenApr 01, 2022HAPLN1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
Cadd
Benign
6.5
Dann
Benign
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs148966419; hg19: chr5-82940369; API