8-22627745-T-C

Variant names:

• chr8-22627745-T-C
• rs900267
• NM_018688.6:c.338+2219A>G

Variant summary

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

The NM_018688.6(BIN3):​c.338+2219A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,184 control chromosomes in the GnomAD database, including 13,016 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 0.41 (13016 hom., cov: 33)
• Consequence: BIN3 NM_018688.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385
• Publications: 7 publications found

Genes affected

BIN3 (HGNC:1054): (bridging integrator 3) The product of this gene is a member of the BAR domain protein family. The encoded protein is comprised solely of a BAR domain which is predicted to form coiled-coil structures and proposed to mediate dimerization, sense and induce membrane curvature, and bind small GTPases. BAR domain proteins have been implicated in endocytosis, intracellular transport, and a diverse set of other processes. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018688.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIN3	NM_018688.6	MANE Select	c.338+2219A>G		intron	N/A	NP_061158.1
	BIN3	NM_001363046.2		c.194+2219A>G		intron	N/A	NP_001349975.1
	BIN3	NR_156436.2		n.408+2219A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIN3	ENST00000276416.11	TSL:1 MANE Select	c.338+2219A>G		intron	N/A	ENSP00000276416.6
	BIN3	ENST00000399977.8	TSL:2	c.194+2219A>G		intron	N/A	ENSP00000382859.4
	BIN3	ENST00000519513.5	TSL:2	c.176+2219A>G		intron	N/A	ENSP00000430423.1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61992 AN: 152066 Hom.: 12991 Cov.: 33

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.408 AC: 62056 AN: 152184 Hom.: 13016 Cov.: 33 AF XY: 0.405 AC XY: 30167 AN XY: 74404

African (AFR) AF: 0.464 AC: 19271 AN: 41502

American (AMR) AF: 0.359 AC: 5496 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1371 AN: 3472

East Asian (EAS) AF: 0.259 AC: 1341 AN: 5178

South Asian (SAS) AF: 0.505 AC: 2436 AN: 4824

European-Finnish (FIN) AF: 0.357 AC: 3781 AN: 10602

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27122 AN: 67984

Other (OTH) AF: 0.404 AC: 852 AN: 2110

Alfa AF: 0.328 Hom.: 1263

Bravo AF: 0.403

Asia WGS AF: 0.422 AC: 1469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.17
PhyloP100		-0.39
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: rs900267; hg19: chr8-22485258;