chr19-51716824-C-G

Variant names:

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

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+144G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0174 in 675,518 control chromosomes in the GnomAD database, including 436 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 0.026 (126 hom., cov: 29)
  • Exomes 𝑓: 0.015 (310 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAS1	NM_001297436.2	MANE Select	c.925+144G>C		intron	N/A	NP_001284365.1	G3V1S7
	HAS1	NM_001523.4		c.928+144G>C		intron	N/A	NP_001514.2	Q92839

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAS1	ENST00000540069.7	TSL:1 MANE Select	c.925+144G>C		intron	N/A	ENSP00000445021.2	G3V1S7
	HAS1	ENST00000601714.5	TSL:1	c.949+144G>C		intron	N/A	ENSP00000472821.1	M0R2V0
	HAS1	ENST00000222115.5	TSL:1	c.928+144G>C		intron	N/A	ENSP00000222115.1	Q92839

Frequencies

GnomAD3 genomes AF: 0.0257 AC: 3900 AN: 151742 Hom.: 125 Cov.: 29

Gnomad AFR AF: 0.0641

Gnomad AMI AF: 0.00879

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0547

Gnomad FIN AF: 0.00133

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00135

Gnomad OTH AF: 0.0226

GnomAD4 exome AF: 0.0150 AC: 7851 AN: 523658 Hom.: 310 AF XY: 0.0162 AC XY: 4497 AN XY: 277858

African (AFR) AF: 0.0680 AC: 1021 AN: 15010

American (AMR) AF: 0.00726 AC: 222 AN: 30562

Ashkenazi Jewish (ASJ) AF: 0.000436 AC: 7 AN: 16064

East Asian (EAS) AF: 0.0941 AC: 3057 AN: 32470

South Asian (SAS) AF: 0.0454 AC: 2487 AN: 54728

European-Finnish (FIN) AF: 0.00141 AC: 48 AN: 34036

Middle Eastern (MID) AF: 0.0242 AC: 56 AN: 2312

European-Non Finnish (NFE) AF: 0.00133 AC: 410 AN: 309380

Other (OTH) AF: 0.0187 AC: 543 AN: 29096

GnomAD4 genome AF: 0.0258 AC: 3923 AN: 151860 Hom.: 126 Cov.: 29 AF XY: 0.0259 AC XY: 1925 AN XY: 74208

African (AFR) AF: 0.0644 AC: 2666 AN: 41368

American (AMR) AF: 0.0143 AC: 218 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.117 AC: 603 AN: 5158

South Asian (SAS) AF: 0.0550 AC: 264 AN: 4804

European-Finnish (FIN) AF: 0.00133 AC: 14 AN: 10538

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00135 AC: 92 AN: 67964

Other (OTH) AF: 0.0238 AC: 50 AN: 2104

Alfa AF: 0.000853 Hom.: 1793

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.40
DANN	Benign	0.66
PhyloP100		-0.053
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: rs11084110; hg19: chr19-52220077;