rs13426725

Positions:

• chr2-127083761-T-C

Variant summary

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

The ENST00000316724.10(BIN1):​c.85-7055A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,184 control chromosomes in the GnomAD database, including 2,424 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 0.17 (2424 hom., cov: 32)
• Consequence: BIN1 ENST00000316724.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320

Genes affected

BIN1 (HGNC:1052): (bridging integrator 1) This gene encodes several isoforms of a nucleocytoplasmic adaptor protein, one of which was initially identified as a MYC-interacting protein with features of a tumor suppressor. Isoforms that are expressed in the central nervous system may be involved in synaptic vesicle endocytosis and may interact with dynamin, synaptojanin, endophilin, and clathrin. Isoforms that are expressed in muscle and ubiquitously expressed isoforms localize to the cytoplasm and nucleus and activate a caspase-independent apoptotic process. Studies in mouse suggest that this gene plays an important role in cardiac muscle development. Alternate splicing of the gene results in several transcript variants encoding different isoforms. Aberrant splice variants expressed in tumor cell lines have also been described. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BIN1	NM_139343.3	c.85-7055A>G		intron_variant		ENST00000316724.10	NP_647593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BIN1	ENST00000316724.10	c.85-7055A>G		intron_variant		1	NM_139343.3	ENSP00000316779

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26479 AN: 152066 Hom.: 2423 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0890

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.174 AC: 26498 AN: 152184 Hom.: 2424 Cov.: 32 AF XY: 0.178 AC XY: 13216 AN XY: 74400

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.0890

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.143

Alfa AF: 0.156 Hom.: 2551

Bravo AF: 0.164

Asia WGS AF: 0.185 AC: 643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.51

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: rs13426725; hg19: chr2-127841337;