chr16-69111573-A-C

Position:

• chr16-69111573-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001199280.2(HAS3):​c.636+1542A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 152,184 control chromosomes in the GnomAD database, including 49,562 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 0.80 (49562 hom., cov: 33)
• Consequence: HAS3 NM_001199280.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730

Genes affected

HAS3 (HGNC:4820): (hyaluronan synthase 3) The protein encoded by this gene is involved in the synthesis of the unbranched glycosaminoglycan hyaluronan, or hyaluronic acid, which is a major constituent of the extracellular matrix. This gene is a member of the NODC/HAS gene family. Compared to the proteins encoded by other members of this gene family, this protein appears to be more of a regulator of hyaluronan synthesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAS3	NM_001199280.2	c.636+1542A>C		intron_variant		ENST00000569188.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAS3	ENST00000569188.6	c.636+1542A>C		intron_variant		2	NM_001199280.2	P1
HAS3	ENST00000219322.7	c.636+1542A>C		intron_variant		1
HAS3	ENST00000306560.1	c.636+1542A>C		intron_variant		1		P1
HAS3	ENST00000566118.5	c.636+1542A>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121769 AN: 152064 Hom.: 49484 Cov.: 33

Gnomad AFR AF: 0.950

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.759

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.798

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.801 AC: 121907 AN: 152184 Hom.: 49562 Cov.: 33 AF XY: 0.795 AC XY: 59096 AN XY: 74372

Gnomad4 AFR AF: 0.950

Gnomad4 AMR AF: 0.753

Gnomad4 ASJ AF: 0.759

Gnomad4 EAS AF: 0.741

Gnomad4 SAS AF: 0.711

Gnomad4 FIN AF: 0.660

Gnomad4 NFE AF: 0.757

Gnomad4 OTH AF: 0.802

Alfa AF: 0.765 Hom.: 35394

Bravo AF: 0.813

Asia WGS AF: 0.766 AC: 2665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.76

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: rs3785079; hg19: chr16-69145476;