chr2-127083761-T-C

Variant names:

• chr2-127083761-T-C
• rs13426725
• NM_139343.3:c.85-7055A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139343.3(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 NM_139343.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320
• Publications: 6 publications found

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]

BIN1 Gene-Disease associations (from GenCC):

• myopathy, centronuclear, 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• centronuclear myopathy

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal dominant centronuclear myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive centronuclear myopathy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BIN1	NM_139343.3	c.85-7055A>G		intron_variant	Intron 1 of 18	ENST00000316724.10	NP_647593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BIN1	ENST00000316724.10	c.85-7055A>G		intron_variant	Intron 1 of 18	1	NM_139343.3	ENSP00000316779.5

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

African (AFR) AF: 0.208 AC: 8634 AN: 41504

American (AMR) AF: 0.145 AC: 2223 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 473 AN: 3470

East Asian (EAS) AF: 0.0890 AC: 461 AN: 5180

South Asian (SAS) AF: 0.231 AC: 1116 AN: 4830

European-Finnish (FIN) AF: 0.224 AC: 2364 AN: 10576

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10710 AN: 68008

Other (OTH) AF: 0.143 AC: 303 AN: 2116

Alfa AF: 0.158 Hom.: 3308

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
PhyloP100		-0.032
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: rs13426725; hg19: chr2-127841337;