2-127094445-G-C

Variant summary

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

The NM_139343.3(BIN1):c.84+12415C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,064 control chromosomes in the GnomAD database, including 3,879 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 0.22 (3879 hom., cov: 33)
• Consequence: BIN1 NM_139343.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.639

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BIN1	NM_139343.3	c.84+12415C>G		intron_variant		ENST00000316724.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BIN1	ENST00000316724.10	c.84+12415C>G		intron_variant		1	NM_139343.3

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33089 AN: 151944 Hom.: 3883 Cov.: 33

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.218 AC: 33095 AN: 152064 Hom.: 3879 Cov.: 33 AF XY: 0.216 AC XY: 16090 AN XY: 74342

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.226

Alfa AF: 0.0890 Hom.: 120

Bravo AF: 0.219

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.6
Dann	Benign	0.59

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: rs10207628; hg19: chr2-127852021;