rs336963

Variant names:

• chr5-83673885-G-A
• rs336963
• NM_001884.4:c.-26-336C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-83673885-G-A
• chr5-83673885-G-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.-26-336C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 215,010 control chromosomes in the GnomAD database, including 13,147 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 0.34 (9160 hom., cov: 33)
  • Exomes 𝑓: 0.34 (3987 hom.)
• Consequence: HAPLN1 NM_001884.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAPLN1	NM_001884.4	MANE Select	c.-26-336C>T		intron	N/A	NP_001875.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAPLN1	ENST00000274341.9	TSL:1 MANE Select	c.-26-336C>T		intron	N/A	ENSP00000274341.4
	HAPLN1	ENST00000508307.5	TSL:3	c.-27+248C>T		intron	N/A	ENSP00000421341.1
	HAPLN1	ENST00000504713.5	TSL:5	c.-26-336C>T		intron	N/A	ENSP00000422522.2

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52157 AN: 152008 Hom.: 9155 Cov.: 33

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.356

GnomAD4 exome AF: 0.344 AC: 21634 AN: 62884 Hom.: 3987 AF XY: 0.350 AC XY: 11319 AN XY: 32338

African (AFR) AF: 0.291 AC: 215 AN: 740

American (AMR) AF: 0.409 AC: 285 AN: 696

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 573 AN: 1774

East Asian (EAS) AF: 0.511 AC: 459 AN: 898

South Asian (SAS) AF: 0.410 AC: 3466 AN: 8450

European-Finnish (FIN) AF: 0.346 AC: 1332 AN: 3846

Middle Eastern (MID) AF: 0.327 AC: 108 AN: 330

European-Non Finnish (NFE) AF: 0.327 AC: 13773 AN: 42146

Other (OTH) AF: 0.355 AC: 1423 AN: 4004

GnomAD4 genome AF: 0.343 AC: 52193 AN: 152126 Hom.: 9160 Cov.: 33 AF XY: 0.345 AC XY: 25641 AN XY: 74380

African (AFR) AF: 0.298 AC: 12347 AN: 41492

American (AMR) AF: 0.390 AC: 5969 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1186 AN: 3468

East Asian (EAS) AF: 0.529 AC: 2736 AN: 5176

South Asian (SAS) AF: 0.418 AC: 2012 AN: 4818

European-Finnish (FIN) AF: 0.341 AC: 3610 AN: 10572

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

European-Non Finnish (NFE) AF: 0.339 AC: 23063 AN: 67988

Other (OTH) AF: 0.362 AC: 765 AN: 2112

Alfa AF: 0.321 Hom.: 4612

Bravo AF: 0.348

Asia WGS AF: 0.507 AC: 1762 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.8
DANN	Benign	0.59
PhyloP100		0.097
PromoterAI		-0.0083	Neutral
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: rs336963; hg19: chr5-82969704;