19-51716766-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001297436.2(HAS1):c.925+202G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 151,560 control chromosomes in the GnomAD database, including 34,854 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 0.67 (34854 hom., cov: 29)
• Consequence: HAS1 NM_001297436.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290

Genes affected

HAS1 (HGNC:4818): (hyaluronan synthase 1) Hyaluronan or hyaluronic acid (HA) is a high molecular weight unbranched polysaccharide synthesized by a wide variety of organisms from bacteria to mammals, and is a constituent of the extracellular matrix. It consists of alternating glucuronic acid and N-acetylglucosamine residues that are linked by beta-1-3 and beta-1-4 glycosidic bonds. HA is synthesized by membrane-bound synthase at the inner surface of the plasma membrane, and the chains are extruded through pore-like structures into the extracellular space. It serves a variety of functions, including space filling, lubrication of joints, and provision of a matrix through which cells can migrate. HA is actively produced during wound healing and tissue repair to provide a framework for ingrowth of blood vessels and fibroblasts. Changes in the serum concentration of HA are associated with inflammatory and degenerative arthropathies such as rheumatoid arthritis. In addition, the interaction of HA with the leukocyte receptor CD44 is important in tissue-specific homing by leukocytes, and overexpression of HA receptors has been correlated with tumor metastasis. HAS1 is a member of the newly identified vertebrate gene family encoding putative hyaluronan synthases, and its amino acid sequence shows significant homology to the hasA gene product of Streptococcus pyogenes, a glycosaminoglycan synthetase (DG42) from Xenopus laevis, and a recently described murine hyaluronan synthase. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAS1	NM_001297436.2	c.925+202G>A		intron_variant		ENST00000540069.7
HAS1	NM_001523.4	c.928+202G>A		intron_variant
HAS1	XM_011526884.3	c.928+202G>A		intron_variant
HAS1	XM_047438719.1	c.925+202G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAS1	ENST00000540069.7	c.925+202G>A		intron_variant		1	NM_001297436.2	A1

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101433 AN: 151442 Hom.: 34823 Cov.: 29

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.652

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

GnomAD4 genome AF: 0.670 AC: 101518 AN: 151560 Hom.: 34854 Cov.: 29 AF XY: 0.678 AC XY: 50184 AN XY: 74044

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.873

Gnomad4 SAS AF: 0.754

Gnomad4 FIN AF: 0.798

Gnomad4 NFE AF: 0.702

Gnomad4 OTH AF: 0.655

Alfa AF: 0.695 Hom.: 62888

Bravo AF: 0.655

Asia WGS AF: 0.801 AC: 2780 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.5
Dann	Benign	0.61

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: rs11084109; hg19: chr19-52220019;