NM_139343.3:c.*479dupA

Variant names:

• chr2-127048046-A-AT
• rs367627116
• NM_139343.3:c.*479dupA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_139343.3(BIN1):​c.*479dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00946 in 188,732 control chromosomes in the GnomAD database, including 19 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0084 (18 hom., cov: 33)
  • Exomes 𝑓: 0.014 (1 hom.)
• Consequence: BIN1 NM_139343.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0084 (1261/150180) while in subpopulation AFR AF= 0.0271 (1111/41064). AF 95% confidence interval is 0.0257. There are 18 homozygotes in gnomad4. There are 616 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 18 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIN1	NM_139343.3	c.*479dupA		3_prime_UTR_variant	Exon 19 of 19	ENST00000316724.10	NP_647593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BIN1	ENST00000316724	c.*479dupA		3_prime_UTR_variant	Exon 19 of 19	1	NM_139343.3	ENSP00000316779.5

Frequencies

GnomAD3 genomes AF: 0.00834 AC: 1252 AN: 150080 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.00145

Gnomad EAS AF: 0.00176

Gnomad SAS AF: 0.00232

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000579

Gnomad OTH AF: 0.00631

GnomAD4 exome AF: 0.0136 AC: 525 AN: 38552 Hom.: 1 Cov.: 0 AF XY: 0.0133 AC XY: 264 AN XY: 19908

Gnomad4 AFR exome AF: 0.0232

Gnomad4 AMR exome AF: 0.0108

Gnomad4 ASJ exome AF: 0.0141

Gnomad4 EAS exome AF: 0.0151

Gnomad4 SAS exome AF: 0.0133

Gnomad4 FIN exome AF: 0.0128

Gnomad4 NFE exome AF: 0.0137

Gnomad4 OTH exome AF: 0.0128

GnomAD4 genome AF: 0.00840 AC: 1261 AN: 150180 Hom.: 18 Cov.: 33 AF XY: 0.00841 AC XY: 616 AN XY: 73240

Gnomad4 AFR AF: 0.0271

Gnomad4 AMR AF: 0.00484

Gnomad4 ASJ AF: 0.00145

Gnomad4 EAS AF: 0.00176

Gnomad4 SAS AF: 0.00212

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000579

Gnomad4 OTH AF: 0.00624

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs367627116; hg19: chr2-127805622;