chr19-51717182-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.06

Publications

5 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 61 gene

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.711G>A	p.Ser237Ser	synonymous	Exon 3 of 5	NP_001284365.1	G3V1S7
	HAS1	NM_001523.4		c.714G>A	p.Ser238Ser	synonymous	Exon 3 of 5	NP_001514.2	Q92839

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HAS1	ENST00000540069.7	TSL:1 MANE Select	c.711G>A	p.Ser237Ser	synonymous	Exon 3 of 5	ENSP00000445021.2	G3V1S7
HAS1	ENST00000601714.5	TSL:1	c.735G>A	p.Ser245Ser	synonymous	Exon 2 of 4	ENSP00000472821.1	M0R2V0
HAS1	ENST00000222115.5	TSL:1	c.714G>A	p.Ser238Ser	synonymous	Exon 3 of 5	ENSP00000222115.1	Q92839

Frequencies

GnomAD3 genomes

AF:

0.0213

AC:

3245

AN:

152086

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0218

AC:

5443

AN:

249112

AF XY:

0.0217

show subpopulations

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 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.:

AF XY:

0.0293

AC XY:

21261

AN XY:

725922

show subpopulations

African (AFR)

AF:

0.00446

AC:

149

AN:

33444

American (AMR)

AF:

0.00684

AC:

306

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00945

AC:

247

AN:

26124

East Asian (EAS)

AF:

0.000202

AC:

AN:

39692

South Asian (SAS)

AF:

0.00848

AC:

731

AN:

86210

European-Finnish (FIN)

AF:

0.0423

AC:

2213

AN:

52290

Middle Eastern (MID)

AF:

0.00416

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0350

AC:

38804

AN:

1110254

Other (OTH)

AF:

0.0274

AC:

1653

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

2010

4020

6031

8041

10051

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1426

2852

4278

5704

7130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0214

AC:

3261

AN:

152204

Hom.:

Cov.:

AF XY:

0.0212

AC XY:

1581

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.00561

AC:

233

AN:

41536

American (AMR)

AF:

0.0113

AC:

173

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0127

AC:

AN:

3472

East Asian (EAS)

AF:

0.000580

AC:

AN:

5170

South Asian (SAS)

AF:

0.00539

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0422

AC:

447

AN:

10590

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0330

AC:

2244

AN:

68008

Other (OTH)

AF:

0.0184

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

163

327

490

654

817

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0303

Hom.:

124

Bravo

AF:

0.0181

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0306

EpiControl

AF:

0.0278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.92

(source)

DANN

Benign

0.81

PhyloP100

-1.1

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over