rs2276582

Positions:

• chr2-127058848-A-G
• chr2-127058848-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_139343.3(BIN1):​c.1002+163T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 152,070 control chromosomes in the GnomAD database, including 22,965 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.53 (22965 hom., cov: 33)
• Consequence: BIN1 NM_139343.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0420

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 2-127058848-A-G is Benign according to our data. Variant chr2-127058848-A-G is described in ClinVar as [Benign]. Clinvar id is 678144.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BIN1	NM_139343.3	c.1002+163T>C		intron_variant		ENST00000316724.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BIN1	ENST00000316724.10	c.1002+163T>C		intron_variant		1	NM_139343.3

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80405 AN: 151950 Hom.: 22909 Cov.: 33

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.530 AC: 80527 AN: 152070 Hom.: 22965 Cov.: 33 AF XY: 0.531 AC XY: 39451 AN XY: 74306

Gnomad4 AFR AF: 0.757

Gnomad4 AMR AF: 0.491

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.503

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.495

Alfa AF: 0.446 Hom.: 14148

Bravo AF: 0.542

Asia WGS AF: 0.550 AC: 1913 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Myopathy, centronuclear, 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.2
DANN	Benign	0.41

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: rs2276582; hg19: chr2-127816424; COSMIC: COSV52119095; COSMIC: COSV52119095;