chr2-127048046-AT-A

Position:

• chr2-127048046-AT-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_139343.3(BIN1):​c.*479del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0255 in 188,788 control chromosomes in the GnomAD database, including 116 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (111 hom., cov: 33)
  • Exomes 𝑓: 0.019 (5 hom.)
• Consequence: BIN1 NM_139343.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.103

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BIN1	NM_139343.3	c.*479del		3_prime_UTR_variant	19/19	ENST00000316724.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BIN1	ENST00000316724.10	c.*479del		3_prime_UTR_variant	19/19	1	NM_139343.3

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 4052 AN: 150064 Hom.: 107 Cov.: 33

Gnomad AFR AF: 0.0673

Gnomad AMI AF: 0.00222

Gnomad AMR AF: 0.0588

Gnomad ASJ AF: 0.000291

Gnomad EAS AF: 0.0195

Gnomad SAS AF: 0.0235

Gnomad FIN AF: 0.000492

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00208

Gnomad OTH AF: 0.0223

GnomAD4 exome AF: 0.0193 AC: 744 AN: 38624 Hom.: 5 Cov.: 0 AF XY: 0.0187 AC XY: 373 AN XY: 19954

Gnomad4 AFR exome AF: 0.0481

Gnomad4 AMR exome AF: 0.0729

Gnomad4 ASJ exome AF: 0.0127

Gnomad4 EAS exome AF: 0.0275

Gnomad4 SAS exome AF: 0.0216

Gnomad4 FIN exome AF: 0.0110

Gnomad4 NFE exome AF: 0.0110

Gnomad4 OTH exome AF: 0.0180

GnomAD4 genome AF: 0.0272 AC: 4079 AN: 150164 Hom.: 111 Cov.: 33 AF XY: 0.0271 AC XY: 1984 AN XY: 73228

Gnomad4 AFR AF: 0.0675

Gnomad4 AMR AF: 0.0594

Gnomad4 ASJ AF: 0.000291

Gnomad4 EAS AF: 0.0194

Gnomad4 SAS AF: 0.0235

Gnomad4 FIN AF: 0.000492

Gnomad4 NFE AF: 0.00208

Gnomad4 OTH AF: 0.0226

Bravo AF: 0.0333

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Myopathy, centronuclear, 2 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs367627116; hg19: chr2-127805622;