rs10942332

Positions:

• chr5-83720449-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001884.4(HAPLN1):​c.-27+340C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 151,818 control chromosomes in the GnomAD database, including 6,707 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 0.29 (6707 hom., cov: 32)
• Consequence: HAPLN1 NM_001884.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.300

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAPLN1	NM_001884.4	c.-27+340C>T		intron_variant		ENST00000274341.9	NP_001875.1
HAPLN1	XM_017009051.2	c.-77+340C>T		intron_variant			XP_016864540.1
HAPLN1	XM_017009053.2	c.-27+340C>T		intron_variant			XP_016864542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAPLN1	ENST00000274341.9	c.-27+340C>T		intron_variant		1	NM_001884.4	ENSP00000274341.4
HAPLN1	ENST00000515590.1	c.-77+340C>T		intron_variant		5		ENSP00000423836.1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43521 AN: 151698 Hom.: 6691 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.287 AC: 43556 AN: 151818 Hom.: 6707 Cov.: 32 AF XY: 0.286 AC XY: 21228 AN XY: 74178

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.333

Alfa AF: 0.310 Hom.: 1802

Bravo AF: 0.288

Asia WGS AF: 0.347 AC: 1203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	11
DANN	Benign	0.68

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

LitVar

Other links and lift over

dbSNP: rs10942332; hg19: chr5-83016268;