Variant rs42082 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001135556.2(DYNC1I1):c.1651-9C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,592,128 control chromosomes in the GnomAD database, including 202,263 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16698 hom., cov: 33)

Exomes 𝑓: 0.50 ( 185565 hom. )

Consequence

DYNC1I1
NM_001135556.2 intron

Scores

Splicing: ADA: 0.0009816

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0410

Variant links:

Genes affected

DYNC1I1 (HGNC:2963): (dynein cytoplasmic 1 intermediate chain 1) Enables spectrin binding activity. Involved in vesicle transport along microtubule. Located in several cellular components, including kinetochore; recycling endosome; and spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

DYNC1I1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 7-96080354-C-A is Benign according to our data. Variant chr7-96080354-C-A is described in ClinVar as [Benign]. Clinvar id is 402812.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNC1I1	NM_001135556.2 linkuse as main transcript	c.1651-9C>A		intron_variant		ENST00000447467.6	NP_001129028.1	O14576-2A4D1I7Q8N542

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNC1I1	ENST00000447467.6 linkuse as main transcript	c.1651-9C>A		intron_variant		1	NM_001135556.2	ENSP00000392337.2		O14576-2

Frequencies

GnomAD3 genomes

AF:

0.458

AC:

69617

AN:

151900

Hom.:

16705

Cov.:

show subpopulations

Gnomad AFR

AF:

0.315

Gnomad AMI

AF:

0.717

Gnomad AMR

AF:

0.461

Gnomad ASJ

AF:

0.600

Gnomad EAS

AF:

0.545

Gnomad SAS

AF:

0.401

Gnomad FIN

AF:

0.516

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.521

Gnomad OTH

AF:

0.500

GnomAD3 exomes

AF:

0.480

AC:

111667

AN:

232724

Hom.:

27902

AF XY:

0.484

AC XY:

60728

AN XY:

125424

show subpopulations

Gnomad AFR exome

AF:

0.311

Gnomad AMR exome

AF:

0.375

Gnomad ASJ exome

AF:

0.617

Gnomad EAS exome

AF:

0.561

Gnomad SAS exome

AF:

0.399

Gnomad FIN exome

AF:

0.508

Gnomad NFE exome

AF:

0.524

Gnomad OTH exome

AF:

0.516

GnomAD4 exome

AF:

0.505

AC:

726597

AN:

1440112

Hom.:

185565

Cov.:

AF XY:

0.502

AC XY:

359320

AN XY:

715134

show subpopulations

Gnomad4 AFR exome

AF:

0.308

Gnomad4 AMR exome

AF:

0.384

Gnomad4 ASJ exome

AF:

0.616

Gnomad4 EAS exome

AF:

0.526

Gnomad4 SAS exome

AF:

0.395

Gnomad4 FIN exome

AF:

0.510

Gnomad4 NFE exome

AF:

0.519

Gnomad4 OTH exome

AF:

0.509

GnomAD4 genome

AF:

0.458

AC:

69609

AN:

152016

Hom.:

16698

Cov.:

AF XY:

0.457

AC XY:

33945

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.314

Gnomad4 AMR

AF:

0.460

Gnomad4 ASJ

AF:

0.600

Gnomad4 EAS

AF:

0.545

Gnomad4 SAS

AF:

0.399

Gnomad4 FIN

AF:

0.516

Gnomad4 NFE

AF:

0.521

Gnomad4 OTH

AF:

0.496

Alfa

AF:

0.489

Hom.:

6226

Bravo

AF:

0.453

Asia WGS

AF:

0.485

AC:

1687

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

DYNC1I1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 26, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

9.2

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00098

dbscSNV1_RF

Benign

0.084

SpliceAI score (max)

0.010

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