rs2479726

Positions:

• chr6-41930358-A-G

Variant summary

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

The NM_004053.4(BYSL):​c.570+88A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 1,500,618 control chromosomes in the GnomAD database, including 411,079 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 0.78 (47027 hom., cov: 30)
  • Exomes 𝑓: 0.73 (364052 hom.)
• Consequence: BYSL NM_004053.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146

Genes affected

BYSL (HGNC:1157): (bystin like) Bystin is expressed as a 2-kb major transcript and a 3.6-kb minor transcript in SNG-M cells and in human trophoblastic teratocarcinoma HT-H cells. Protein binding assays determined that bystin binds directly to trophinin and tastin, and that binding is enhanced when cytokeratins 8 and 18 are present. Immunocytochemistry of HT-H cells showed that bystin colocalizes with trophinin, tastin, and the cytokeratins, suggesting that these molecules form a complex in trophectoderm cells at the time of implantation. Using immunohistochemistry it was determined that trophinin and bystin are found in the placenta from the sixth week of pregnancy. Both proteins were localized in the cytoplasm of the syncytiotrophoblast in the chorionic villi and in endometrial decidual cells at the uteroplacental interface. After week 10, the levels of trophinin, tastin, and bystin decreased and then disappeared from placental villi. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BYSL	NM_004053.4	c.570+88A>G		intron_variant		ENST00000230340.9	NP_004044.3
BYSL	XM_047419281.1	c.324+88A>G		intron_variant			XP_047275237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BYSL	ENST00000230340.9	c.570+88A>G		intron_variant		1	NM_004053.4	ENSP00000230340	P1
BYSL	ENST00000372996.2	c.241+88A>G		intron_variant, NMD_transcript_variant		5		ENSP00000362087
BYSL	ENST00000489290.1	c.432-277A>G		intron_variant, NMD_transcript_variant		3		ENSP00000417813
BYSL	ENST00000475702.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118513 AN: 151924 Hom.: 46977 Cov.: 30

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.756

GnomAD4 exome AF: 0.733 AC: 989054 AN: 1348576 Hom.: 364052 Cov.: 24 AF XY: 0.733 AC XY: 486687 AN XY: 663888

Gnomad4 AFR exome AF: 0.946

Gnomad4 AMR exome AF: 0.649

Gnomad4 ASJ exome AF: 0.674

Gnomad4 EAS exome AF: 0.790

Gnomad4 SAS exome AF: 0.729

Gnomad4 FIN exome AF: 0.749

Gnomad4 NFE exome AF: 0.728

Gnomad4 OTH exome AF: 0.738

GnomAD4 genome AF: 0.780 AC: 118618 AN: 152042 Hom.: 47027 Cov.: 30 AF XY: 0.780 AC XY: 57942 AN XY: 74280

Gnomad4 AFR AF: 0.940

Gnomad4 AMR AF: 0.688

Gnomad4 ASJ AF: 0.659

Gnomad4 EAS AF: 0.788

Gnomad4 SAS AF: 0.730

Gnomad4 FIN AF: 0.737

Gnomad4 NFE AF: 0.721

Gnomad4 OTH AF: 0.755

Alfa AF: 0.734 Hom.: 20130

Bravo AF: 0.784

Asia WGS AF: 0.759 AC: 2639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.75
DANN	Benign	0.58

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: rs2479726; hg19: chr6-41898096;