rs10207628

Variant names:

• chr2-127094445-G-A
• rs10207628
• NM_139343.3:c.84+12415C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-127094445-G-A
• chr2-127094445-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_139343.3(BIN1):​c.84+12415C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00603 in 152,114 control chromosomes in the GnomAD database, including 14 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 0.0060 (14 hom., cov: 33)
• Consequence: BIN1 NM_139343.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.639
• Publications: 15 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=-0.98).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00603 (918/152114) while in subpopulation NFE AF = 0.00412 (280/67976). AF 95% confidence interval is 0.00372. There are 14 homozygotes in GnomAd4. There are 606 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 AR,AD,SD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139343.3. 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.84+12415C>T		intron	N/A	NP_647593.1	O00499-1
	BIN1	NM_001320641.2		c.84+12415C>T		intron	N/A	NP_001307570.1
	BIN1	NM_139344.3		c.84+12415C>T		intron	N/A	NP_647594.1	O00499-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIN1	ENST00000316724.10	TSL:1 MANE Select	c.84+12415C>T		intron	N/A	ENSP00000316779.5	O00499-1
	BIN1	ENST00000357970.7	TSL:1	c.84+12415C>T		intron	N/A	ENSP00000350654.3	O00499-5
	BIN1	ENST00000346226.7	TSL:1	c.84+12415C>T		intron	N/A	ENSP00000315411.3	O00499-2

Frequencies

GnomAD3 genomes AF: 0.00604 AC: 918 AN: 151994 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.00126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0535

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00412

Gnomad OTH AF: 0.00336

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

GnomAD4 genome AF: 0.00603 AC: 918 AN: 152114 Hom.: 14 Cov.: 33 AF XY: 0.00815 AC XY: 606 AN XY: 74370

African (AFR) AF: 0.00125 AC: 52 AN: 41480

American (AMR) AF: 0.000654 AC: 10 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.0535 AC: 566 AN: 10578

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00412 AC: 280 AN: 67976

Other (OTH) AF: 0.00332 AC: 7 AN: 2108

Alfa AF: 0.00499 Hom.: 120

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.4
DANN	Benign	0.64
PhyloP100		0.64
Mutation Taster		=100/0	polymorphism

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: rs10207628; hg19: chr2-127852021;