12-51289206-T-A

Variant names:

• chr12-51289206-T-A
• rs12227330
• NM_016293.4:c.1516-1018A>T

Variant summary

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

The NM_016293.4(BIN2):​c.1516-1018A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 152,016 control chromosomes in the GnomAD database, including 64,201 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 0.91 (64201 hom., cov: 31)
• Consequence: BIN2 NM_016293.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155
• Publications: 1 publications found

Genes affected

BIN2 (HGNC:1053): (bridging integrator 2) Enables phospholipid binding activity. Involved in several processes, including phagocytosis, engulfment; plasma membrane tubulation; and podosome assembly. Located in plasma membrane and podosome. Colocalizes with phagocytic cup. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016293.4. 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
	BIN2	NM_016293.4	MANE Select	c.1516-1018A>T		intron	N/A	NP_057377.4
	BIN2	NM_001364779.1		c.1513-1018A>T		intron	N/A	NP_001351708.1
	BIN2	NM_001290007.2		c.1438-1018A>T		intron	N/A	NP_001276936.1	Q9UBW5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIN2	ENST00000615107.6	TSL:1 MANE Select	c.1516-1018A>T		intron	N/A	ENSP00000483983.2	Q9UBW5-1
	BIN2	ENST00000605039.5	TSL:1	n.2138-1018A>T		intron	N/A
	BIN2	ENST00000871152.1		c.1513-1018A>T		intron	N/A	ENSP00000541211.1

Frequencies

GnomAD3 genomes AF: 0.909 AC: 138002 AN: 151898 Hom.: 64170 Cov.: 31

Gnomad AFR AF: 0.680

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.967

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.941

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

GnomAD4 genome AF: 0.908 AC: 138089 AN: 152016 Hom.: 64201 Cov.: 31 AF XY: 0.913 AC XY: 67891 AN XY: 74320

African (AFR) AF: 0.680 AC: 28128 AN: 41358

American (AMR) AF: 0.967 AC: 14765 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 3463 AN: 3468

East Asian (EAS) AF: 1.00 AC: 5184 AN: 5184

South Asian (SAS) AF: 1.00 AC: 4820 AN: 4822

European-Finnish (FIN) AF: 1.00 AC: 10604 AN: 10604

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67943 AN: 68004

Other (OTH) AF: 0.942 AC: 1981 AN: 2104

Alfa AF: 0.947 Hom.: 8584

Bravo AF: 0.895

Asia WGS AF: 0.984 AC: 3422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.3
DANN	Benign	0.62
PhyloP100		0.15
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: rs12227330; hg19: chr12-51682990;