2-127082205-C-A

Position:

• chr2-127082205-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_139343.3(BIN1):​c.85-5499G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 151,680 control chromosomes in the GnomAD database, including 7,639 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.31 (7639 hom., cov: 30)
• Consequence: BIN1 NM_139343.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.49

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-127082205-C-A is Benign according to our data. Variant chr2-127082205-C-A is described in ClinVar as [Benign]. Clinvar id is 1251745.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BIN1	NM_139343.3	c.85-5499G>T		intron_variant		ENST00000316724.10	NP_647593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BIN1	ENST00000316724.10	c.85-5499G>T		intron_variant		1	NM_139343.3	ENSP00000316779.5

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47389 AN: 151562 Hom.: 7628 Cov.: 30

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.313 AC: 47449 AN: 151680 Hom.: 7639 Cov.: 30 AF XY: 0.314 AC XY: 23272 AN XY: 74096

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.293

Alfa AF: 0.327 Hom.: 16374

Bravo AF: 0.301

Asia WGS AF: 0.300 AC: 1043 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.89
DANN	Benign	0.79

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: rs10194375; hg19: chr2-127839781;