rs725859

Variant names:

• chr7-123784529-G-T
• rs725859
• XM_047420093.1:c.-1823-2805G>T

Variant summary

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

The XM_047420093.1(HYAL4):​c.-1823-2805G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0658 in 152,244 control chromosomes in the GnomAD database, including 417 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 0.066 (417 hom., cov: 32)
• Consequence: HYAL4 XM_047420093.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204
• Publications: 4 publications found

Genes affected

HYAL4 (HGNC:5323): (hyaluronidase 4) This gene encodes a protein which is similar in structure to hyaluronidases but lacks hyaluronidase activity. The encoded protein acts as a chondroitin-sulfate-specific endo-beta-N-acetylgalactosaminidase; that is, it exhibits hydrolytic activity toward chondroitin sulfate chains and degrades them into oligosaccharides. Proteoglycans are formed by the covalent linkage of chondroitin sulfate chains to protein. Proteoglycans are ubiquitous components of the extracellular matrix of connective tissues and are also found at the surface of many cell types where they participate in a variety of cellular processes such as cell proliferation, differentiation, migration, cell-cell recognition, extracellular matrix deposition, and tissue morphogenesis. The expression of this gene is highest in testes and placenta. [provided by RefSeq, Apr 2019]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYAL4	XM_047420093.1	c.-1823-2805G>T		intron_variant	Intron 1 of 7		XP_047276049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.0659 AC: 10025 AN: 152124 Hom.: 417 Cov.: 32

Gnomad AFR AF: 0.0249

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0567

Gnomad ASJ AF: 0.0769

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.0499

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.0791

Gnomad OTH AF: 0.0664

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

GnomAD4 genome AF: 0.0658 AC: 10022 AN: 152244 Hom.: 417 Cov.: 32 AF XY: 0.0684 AC XY: 5091 AN XY: 74432

African (AFR) AF: 0.0249 AC: 1033 AN: 41564

American (AMR) AF: 0.0566 AC: 865 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0769 AC: 267 AN: 3472

East Asian (EAS) AF: 0.114 AC: 587 AN: 5170

South Asian (SAS) AF: 0.0501 AC: 242 AN: 4828

European-Finnish (FIN) AF: 0.130 AC: 1373 AN: 10580

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0791 AC: 5377 AN: 68014

Other (OTH) AF: 0.0658 AC: 139 AN: 2114

Alfa AF: 0.0669 Hom.: 76

Bravo AF: 0.0604

Asia WGS AF: 0.0890 AC: 309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.77
PhyloP100		0.20

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs725859; hg19: chr7-123424583;