2-127084193-C-T

Variant names:

• chr2-127084193-C-T
• rs10200967
• NM_139343.3:c.85-7487G>A

Variant summary

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

The NM_001320642.1(BIN1):​c.-602G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 152,066 control chromosomes in the GnomAD database, including 42,496 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 0.75 (42496 hom., cov: 32)
• Consequence: BIN1 NM_001320642.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.664
• Publications: 14 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):

• centronuclear myopathy

  Inheritance: AD, AR, SD Classification: DEFINITIVE, LIMITED Submitted by: ClinGen
• myopathy, centronuclear, 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320642.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIN1	NM_139343.3	MANE Select	c.85-7487G>A		intron	N/A	NP_647593.1	O00499-1
	BIN1	NM_001320642.1		c.-602G>A		5_prime_UTR	Exon 1 of 19	NP_001307571.1	O00499
	BIN1	NM_001320641.2		c.85-7487G>A		intron	N/A	NP_001307570.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIN1	ENST00000316724.10	TSL:1 MANE Select	c.85-7487G>A		intron	N/A	ENSP00000316779.5	O00499-1
	BIN1	ENST00000357970.7	TSL:1	c.85-7487G>A		intron	N/A	ENSP00000350654.3	O00499-5
	BIN1	ENST00000346226.7	TSL:1	c.85-7487G>A		intron	N/A	ENSP00000315411.3	O00499-2

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113208 AN: 151948 Hom.: 42443 Cov.: 32

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.749

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.745 AC: 113321 AN: 152066 Hom.: 42496 Cov.: 32 AF XY: 0.743 AC XY: 55245 AN XY: 74316

African (AFR) AF: 0.789 AC: 32726 AN: 41476

American (AMR) AF: 0.722 AC: 11042 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2400 AN: 3468

East Asian (EAS) AF: 0.502 AC: 2587 AN: 5154

South Asian (SAS) AF: 0.736 AC: 3540 AN: 4812

European-Finnish (FIN) AF: 0.727 AC: 7675 AN: 10562

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.749 AC: 50927 AN: 67978

Other (OTH) AF: 0.728 AC: 1537 AN: 2112

Alfa AF: 0.744 Hom.: 77995

Bravo AF: 0.741

Asia WGS AF: 0.673 AC: 2344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.2
DANN	Benign	0.62
PhyloP100		0.66
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: rs10200967; hg19: chr2-127841769;