rs61736495

Positions:

• chr19-51717182-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_001297436.2(HAS1):​c.711G>A​(p.Ser237Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0294 in 1,611,028 control chromosomes in the GnomAD database, including 900 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 0.021 (61 hom., cov: 32)
  • Exomes 𝑓: 0.030 (839 hom.)
• Consequence: HAS1 NM_001297436.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=-1.06 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0214 (3261/152204) while in subpopulation NFE AF= 0.033 (2244/68008). AF 95% confidence interval is 0.0319. There are 61 homozygotes in gnomad4. There are 1581 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 61 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAS1	NM_001297436.2	c.711G>A	p.Ser237Ser	synonymous_variant	3/5	ENST00000540069.7	NP_001284365.1
HAS1	NM_001523.4	c.714G>A	p.Ser238Ser	synonymous_variant	3/5		NP_001514.2
HAS1	XM_011526884.3	c.714G>A	p.Ser238Ser	synonymous_variant	3/4		XP_011525186.1
HAS1	XM_047438719.1	c.711G>A	p.Ser237Ser	synonymous_variant	3/4		XP_047294675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAS1	ENST00000540069.7	c.711G>A	p.Ser237Ser	synonymous_variant	3/5	1	NM_001297436.2	ENSP00000445021.2

Frequencies

GnomAD3 genomes AF: 0.0213 AC: 3245 AN: 152086 Hom.: 56 Cov.: 32

Gnomad AFR AF: 0.00563

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.00539

Gnomad FIN AF: 0.0422

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0330

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.0218 AC: 5443 AN: 249112 Hom.: 90 AF XY: 0.0217 AC XY: 2929 AN XY: 134842

Gnomad AFR exome AF: 0.00513

Gnomad AMR exome AF: 0.00715

Gnomad ASJ exome AF: 0.0101

Gnomad EAS exome AF: 0.000164

Gnomad SAS exome AF: 0.00827

Gnomad FIN exome AF: 0.0456

Gnomad NFE exome AF: 0.0330

Gnomad OTH exome AF: 0.0173

GnomAD4 exome AF: 0.0303 AC: 44135 AN: 1458824 Hom.: 839 Cov.: 31 AF XY: 0.0293 AC XY: 21261 AN XY: 725922

Gnomad4 AFR exome AF: 0.00446

Gnomad4 AMR exome AF: 0.00684

Gnomad4 ASJ exome AF: 0.00945

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.00848

Gnomad4 FIN exome AF: 0.0423

Gnomad4 NFE exome AF: 0.0350

Gnomad4 OTH exome AF: 0.0274

GnomAD4 genome AF: 0.0214 AC: 3261 AN: 152204 Hom.: 61 Cov.: 32 AF XY: 0.0212 AC XY: 1581 AN XY: 74416

Gnomad4 AFR AF: 0.00561

Gnomad4 AMR AF: 0.0113

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.00539

Gnomad4 FIN AF: 0.0422

Gnomad4 NFE AF: 0.0330

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.0285 Hom.: 38

Bravo AF: 0.0181

Asia WGS AF: 0.0120 AC: 43 AN: 3478

EpiCase AF: 0.0306

EpiControl AF: 0.0278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.92
DANN	Benign	0.81

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: rs61736495; hg19: chr19-52220435; COSMIC: COSV55789610; COSMIC: COSV55789610;