Variant 8-22630437-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018688.6(BIN3):c.297+5C>T variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00346 in 1,613,834 control chromosomes in the GnomAD database, including 160 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.018 ( 76 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 84 hom. )

Consequence

BIN3
NM_018688.6 splice_donor_5th_base, intron

Scores

Splicing: ADA: 0.0004558

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.428

Variant links:

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]

BIN3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 8-22630437-G-A is Benign according to our data. Variant chr8-22630437-G-A is described in ClinVar as [Benign]. Clinvar id is 776292.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BIN3	NM_018688.6 linkuse as main transcript	c.297+5C>T		splice_donor_5th_base_variant, intron_variant		ENST00000276416.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BIN3	ENST00000276416.11 linkuse as main transcript	c.297+5C>T		splice_donor_5th_base_variant, intron_variant		1	NM_018688.6	P1	Q9NQY0-1

Frequencies

GnomAD3 genomes

AF:

0.0178

AC:

2708

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0601

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0106

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.00460

AC:

1145

AN:

249064

Hom.:

AF XY:

0.00358

AC XY:

483

AN XY:

135102

show subpopulations

Gnomad AFR exome

AF:

0.0610

Gnomad AMR exome

AF:

0.00357

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000478

Gnomad OTH exome

AF:

0.00265

GnomAD4 exome

AF:

0.00196

AC:

2870

AN:

1461554

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

1279

AN XY:

727050

show subpopulations

Gnomad4 AFR exome

AF:

0.0610

Gnomad4 AMR exome

AF:

0.00494

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000206

Gnomad4 OTH exome

AF:

0.00558

GnomAD4 genome

AF:

0.0179

AC:

2719

AN:

152280

Hom.:

Cov.:

AF XY:

0.0172

AC XY:

1282

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0602

Gnomad4 AMR

AF:

0.0106

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.00876

Hom.:

Bravo

AF:

0.0218

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00046

dbscSNV1_RF

Benign

0.034

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over