19-51716685-A-T

Variant names:

• chr19-51716685-A-T
• rs11669079
• NM_001297436.2:c.925+283T>A

Variant summary

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

The NM_001297436.2(HAS1):​c.925+283T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 151,460 control chromosomes in the GnomAD database, including 34,914 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 (34914 hom., cov: 29)
• Consequence: HAS1 NM_001297436.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.939
• Publications: 1 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• 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 rank	MANE	Protein	UniProt
HAS1	NM_001297436.2	c.925+283T>A		intron_variant	Intron 3 of 4	ENST00000540069.7	NP_001284365.1
HAS1	NM_001523.4	c.928+283T>A		intron_variant	Intron 3 of 4		NP_001514.2
HAS1	XM_011526884.3	c.928+283T>A		intron_variant	Intron 3 of 3		XP_011525186.1
HAS1	XM_047438719.1	c.925+283T>A		intron_variant	Intron 3 of 3		XP_047294675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAS1	ENST00000540069.7	c.925+283T>A		intron_variant	Intron 3 of 4	1	NM_001297436.2	ENSP00000445021.2

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101530 AN: 151342 Hom.: 34883 Cov.: 29

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.683

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.671 AC: 101615 AN: 151460 Hom.: 34914 Cov.: 29 AF XY: 0.679 AC XY: 50223 AN XY: 73988

African (AFR) AF: 0.522 AC: 21496 AN: 41148

American (AMR) AF: 0.751 AC: 11437 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2404 AN: 3466

East Asian (EAS) AF: 0.872 AC: 4480 AN: 5136

South Asian (SAS) AF: 0.756 AC: 3627 AN: 4800

European-Finnish (FIN) AF: 0.798 AC: 8381 AN: 10496

Middle Eastern (MID) AF: 0.697 AC: 202 AN: 290

European-Non Finnish (NFE) AF: 0.702 AC: 47689 AN: 67886

Other (OTH) AF: 0.657 AC: 1380 AN: 2100

Alfa AF: 0.679 Hom.: 4175

Bravo AF: 0.656

Asia WGS AF: 0.801 AC: 2783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.9
DANN	Benign	0.87
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11669079; hg19: chr19-52219938;