rs4731120

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYAL4	XM_047420093.1	c.-1824+7433A>C		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: 0.0660 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

Gnomad4 AFR AF: 0.0255

Gnomad4 AMR AF: 0.0555

Gnomad4 ASJ AF: 0.0769

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.0506

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.0789

Gnomad4 OTH AF: 0.0662

Alfa AF: 0.0781 Hom.: 636

Bravo AF: 0.0605

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	-0.99
CADD	Benign	0.32
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4731120; hg19: chr7-123411223;