12-51321897-T-G

Variant names:

• chr12-51321897-T-G
• rs4762041
• NM_016293.4:c.81+2125A>C

Variant summary

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

The NM_016293.4(BIN2):​c.81+2125A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 152,184 control chromosomes in the GnomAD database, including 8,491 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 0.32 (8491 hom., cov: 33)
• Consequence: BIN2 NM_016293.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239
• Publications: 9 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=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.433 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.81+2125A>C		intron	N/A	NP_057377.4
	BIN2	NM_001364779.1		c.81+2125A>C		intron	N/A	NP_001351708.1
	BIN2	NM_001290007.2		c.3+2616A>C		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.81+2125A>C		intron	N/A	ENSP00000483983.2	Q9UBW5-1
	BIN2	ENST00000605039.5	TSL:1	n.133+2125A>C		intron	N/A
	BIN2	ENST00000871152.1		c.81+2125A>C		intron	N/A	ENSP00000541211.1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49291 AN: 152066 Hom.: 8477 Cov.: 33

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.324 AC: 49369 AN: 152184 Hom.: 8491 Cov.: 33 AF XY: 0.324 AC XY: 24095 AN XY: 74410

African (AFR) AF: 0.438 AC: 18163 AN: 41480

American (AMR) AF: 0.319 AC: 4878 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1120 AN: 3472

East Asian (EAS) AF: 0.387 AC: 2009 AN: 5188

South Asian (SAS) AF: 0.298 AC: 1436 AN: 4824

European-Finnish (FIN) AF: 0.227 AC: 2406 AN: 10598

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18492 AN: 68004

Other (OTH) AF: 0.299 AC: 633 AN: 2114

Alfa AF: 0.289 Hom.: 10745

Bravo AF: 0.336

Asia WGS AF: 0.363 AC: 1262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.8
DANN	Benign	0.77
PhyloP100		-0.24
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: rs4762041; hg19: chr12-51715681;