chr8-22627745-T-C

Position:

• chr8-22627745-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BIN3	NM_018688.6	c.338+2219A>G		intron_variant		ENST00000276416.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BIN3	ENST00000276416.11	c.338+2219A>G		intron_variant		1	NM_018688.6	P1

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

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.357

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.404

Alfa AF: 0.322 Hom.: 1188

Bravo AF: 0.403

Asia WGS AF: 0.422 AC: 1469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.17

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: rs900267; hg19: chr8-22485258;