rs4731120

Variant names:

• chr7-123771169-A-C
• rs4731120
• XM_047420093.1:c.-1824+7433A>C

Variant summary

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

The XM_047420093.1(HYAL4):​c.-1824+7433A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.066 in 152,236 control chromosomes in the GnomAD database, including 421 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 (421 hom., cov: 32)
• Consequence: HYAL4 XM_047420093.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 16 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.0660 AC: 10045 AN: 152118 Hom.: 421 Cov.: 32

Gnomad AFR AF: 0.0255

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0557

Gnomad ASJ AF: 0.0769

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0503

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0789

Gnomad OTH AF: 0.0669

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

GnomAD4 genome AF: 0.0660 AC: 10042 AN: 152236 Hom.: 421 Cov.: 32 AF XY: 0.0685 AC XY: 5098 AN XY: 74440

African (AFR) AF: 0.0255 AC: 1061 AN: 41562

American (AMR) AF: 0.0555 AC: 849 AN: 15288

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

East Asian (EAS) AF: 0.114 AC: 592 AN: 5174

South Asian (SAS) AF: 0.0506 AC: 244 AN: 4824

European-Finnish (FIN) AF: 0.131 AC: 1384 AN: 10598

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

European-Non Finnish (NFE) AF: 0.0789 AC: 5366 AN: 67998

Other (OTH) AF: 0.0662 AC: 140 AN: 2114

Alfa AF: 0.0760 Hom.: 1537

Bravo AF: 0.0605

Asia WGS AF: 0.0890 AC: 309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.32
DANN	Benign	0.41
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs4731120; hg19: chr7-123411223;