19-51716824-C-A

Variant names:

• chr19-51716824-C-A
• rs11084110
• NM_001297436.2:c.925+144G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001297436.2(HAS1):​c.925+144G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000191 in 523,692 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 29)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: HAS1 NM_001297436.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530
• Publications: 8 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297436.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAS1	NM_001297436.2	MANE Select	c.925+144G>T		intron	N/A	NP_001284365.1
	HAS1	NM_001523.4		c.928+144G>T		intron	N/A	NP_001514.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAS1	ENST00000540069.7	TSL:1 MANE Select	c.925+144G>T		intron	N/A	ENSP00000445021.2
	HAS1	ENST00000601714.5	TSL:1	c.949+144G>T		intron	N/A	ENSP00000472821.1
	HAS1	ENST00000222115.5	TSL:1	c.928+144G>T		intron	N/A	ENSP00000222115.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000191 AC: 1 AN: 523692 Hom.: 0 AF XY: 0.00000360 AC XY: 1 AN XY: 277876

African (AFR) AF: 0.00 AC: 0 AN: 15018

American (AMR) AF: 0.00 AC: 0 AN: 30564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16064

East Asian (EAS) AF: 0.00 AC: 0 AN: 32484

South Asian (SAS) AF: 0.0000183 AC: 1 AN: 54734

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 309380

Other (OTH) AF: 0.00 AC: 0 AN: 29096

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.38
DANN	Benign	0.72
PhyloP100		-0.053

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: rs11084110; hg19: chr19-52220077;