5-83642908-C-A

Variant names:

• chr5-83642908-C-A
• rs4703570
• NM_001884.4:c.776-1123G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001884.4(HAPLN1):​c.776-1123G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 152,094 control chromosomes in the GnomAD database, including 42,076 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 0.74 (42076 hom., cov: 32)
• Consequence: HAPLN1 NM_001884.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAPLN1	NM_001884.4	c.776-1123G>T		intron_variant	Intron 4 of 4	ENST00000274341.9	NP_001875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAPLN1	ENST00000274341.9	c.776-1123G>T		intron_variant	Intron 4 of 4	1	NM_001884.4	ENSP00000274341.4

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112256 AN: 151974 Hom.: 42021 Cov.: 32

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.931

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.752

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

GnomAD4 genome AF: 0.739 AC: 112369 AN: 152094 Hom.: 42076 Cov.: 32 AF XY: 0.739 AC XY: 54913 AN XY: 74334

African (AFR) AF: 0.862 AC: 35788 AN: 41514

American (AMR) AF: 0.756 AC: 11558 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 2593 AN: 3468

East Asian (EAS) AF: 0.587 AC: 3028 AN: 5156

South Asian (SAS) AF: 0.730 AC: 3523 AN: 4828

European-Finnish (FIN) AF: 0.656 AC: 6927 AN: 10556

Middle Eastern (MID) AF: 0.740 AC: 216 AN: 292

European-Non Finnish (NFE) AF: 0.681 AC: 46301 AN: 67970

Other (OTH) AF: 0.750 AC: 1586 AN: 2116

Alfa AF: 0.700 Hom.: 52147

Bravo AF: 0.749

Asia WGS AF: 0.684 AC: 2375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.0
DANN	Benign	0.46
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs4703570; hg19: chr5-82938727; COSMIC: COSV57146256; COSMIC: COSV57146256;