12-51321897-T-G

Position:

• chr12-51321897-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BIN2	NM_016293.4	c.81+2125A>C		intron_variant		ENST00000615107.6	NP_057377.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BIN2	ENST00000615107.6	c.81+2125A>C		intron_variant		1	NM_016293.4	ENSP00000483983	P1

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

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.299

Alfa AF: 0.283 Hom.: 8092

Bravo AF: 0.336

Asia WGS AF: 0.363 AC: 1262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.8
DANN	Benign	0.77

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: rs4762041; hg19: chr12-51715681;