Variant rs11084111 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001297436.2(HAS1):c.795C>T(p.Asp265Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,613,330 control chromosomes in the GnomAD database, including 11,932 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 0.12 ( 1392 hom., cov: 32)

Exomes 𝑓: 0.10 ( 10540 hom. )

Consequence

HAS1
NM_001297436.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.476

Variant links:

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]

HAS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP7

Synonymous conserved (PhyloP=-0.476 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAS1	NM_001297436.2 linkuse as main transcript	c.795C>T	p.Asp265Asp	synonymous_variant	3/5	ENST00000540069.7	NP_001284365.1	G3V1S7Q8IYH3D2N2G5
HAS1	NM_001523.4 linkuse as main transcript	c.798C>T	p.Asp266Asp	synonymous_variant	3/5		NP_001514.2	Q92839Q8IYH3D2N2G5
HAS1	XM_011526884.3 linkuse as main transcript	c.798C>T	p.Asp266Asp	synonymous_variant	3/4		XP_011525186.1
HAS1	XM_047438719.1 linkuse as main transcript	c.795C>T	p.Asp265Asp	synonymous_variant	3/4		XP_047294675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAS1	ENST00000540069.7 linkuse as main transcript	c.795C>T	p.Asp265Asp	synonymous_variant	3/5	1	NM_001297436.2	ENSP00000445021.2		G3V1S7

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18138

AN:

151878

Hom.:

1388

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.421

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0862

Gnomad OTH

AF:

0.125

GnomAD3 exomes

AF:

0.132

AC:

33100

AN:

251296

Hom.:

3225

AF XY:

0.127

AC XY:

17217

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.136

Gnomad AMR exome

AF:

0.122

Gnomad ASJ exome

AF:

0.139

Gnomad EAS exome

AF:

0.445

Gnomad SAS exome

AF:

0.0969

Gnomad FIN exome

AF:

0.138

Gnomad NFE exome

AF:

0.0912

Gnomad OTH exome

AF:

0.123

GnomAD4 exome

AF:

0.104

AC:

152303

AN:

1461334

Hom.:

10540

Cov.:

AF XY:

0.104

AC XY:

75575

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.135

Gnomad4 AMR exome

AF:

0.120

Gnomad4 ASJ exome

AF:

0.136

Gnomad4 EAS exome

AF:

0.429

Gnomad4 SAS exome

AF:

0.0965

Gnomad4 FIN exome

AF:

0.137

Gnomad4 NFE exome

AF:

0.0889

Gnomad4 OTH exome

AF:

0.114

GnomAD4 genome

AF:

0.120

AC:

18164

AN:

151996

Hom.:

1392

Cov.:

AF XY:

0.124

AC XY:

9182

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.137

Gnomad4 AMR

AF:

0.113

Gnomad4 ASJ

AF:

0.128

Gnomad4 EAS

AF:

0.421

Gnomad4 SAS

AF:

0.103

Gnomad4 FIN

AF:

0.142

Gnomad4 NFE

AF:

0.0862

Gnomad4 OTH

AF:

0.124

Alfa

AF:

0.0959

Hom.:

1041

Bravo

AF:

0.120

Asia WGS

AF:

0.237

AC:

824

AN:

3478

EpiCase

AF:

0.0816

EpiControl

AF:

0.0858

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.82

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over