rs2479726

Variant names:

• chr6-41930358-A-G
• rs2479726
• NM_004053.4:c.570+88A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004053.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BYSL	NM_004053.4	MANE Select	c.570+88A>G		intron	N/A	NP_004044.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BYSL	ENST00000230340.9	TSL:1 MANE Select	c.570+88A>G		intron	N/A	ENSP00000230340.4
	BYSL	ENST00000715726.2		c.570+88A>G		intron	N/A	ENSP00000520508.1
	BYSL	ENST00000372996.2	TSL:5	n.240+88A>G		intron	N/A	ENSP00000362087.2

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

African (AFR) AF: 0.946 AC: 28585 AN: 30204

American (AMR) AF: 0.649 AC: 19234 AN: 29658

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 14704 AN: 21800

East Asian (EAS) AF: 0.790 AC: 29396 AN: 37200

South Asian (SAS) AF: 0.729 AC: 54076 AN: 74150

European-Finnish (FIN) AF: 0.749 AC: 35796 AN: 47808

Middle Eastern (MID) AF: 0.678 AC: 3062 AN: 4518

European-Non Finnish (NFE) AF: 0.728 AC: 763121 AN: 1047564

Other (OTH) AF: 0.738 AC: 41080 AN: 55674

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

African (AFR) AF: 0.940 AC: 39005 AN: 41498

American (AMR) AF: 0.688 AC: 10509 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2285 AN: 3468

East Asian (EAS) AF: 0.788 AC: 4066 AN: 5160

South Asian (SAS) AF: 0.730 AC: 3517 AN: 4820

European-Finnish (FIN) AF: 0.737 AC: 7776 AN: 10546

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.721 AC: 49023 AN: 67964

Other (OTH) AF: 0.755 AC: 1594 AN: 2112

Alfa AF: 0.733 Hom.: 22147

Bravo AF: 0.784

Asia WGS AF: 0.759 AC: 2639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.75
DANN	Benign	0.58
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2479726; hg19: chr6-41898096;