Variant 7-95804844-C-G 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.108+7C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.095 in 1,550,238 control chromosomes in the GnomAD database, including 7,489 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 0.081 ( 608 hom., cov: 32)

Exomes 𝑓: 0.097 ( 6881 hom. )

Consequence

DYNC1I1
NM_001135556.2 splice_region, intron

Scores

Splicing: ADA: 0.0001070

Clinical Significance

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

Conservation

PhyloP100: -2.52

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=-0.82).

BP6

Variant 7-95804844-C-G is Benign according to our data. Variant chr7-95804844-C-G is described in ClinVar as [Benign]. Clinvar id is 402810.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYNC1I1	NM_001135556.2 linkuse as main transcript	c.108+7C>G		splice_region_variant, intron_variant		ENST00000447467.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYNC1I1	ENST00000447467.6 linkuse as main transcript	c.108+7C>G		splice_region_variant, intron_variant		1	NM_001135556.2	P3	O14576-2

Frequencies

GnomAD3 genomes

AF:

0.0813

AC:

12341

AN:

151888

Hom.:

609

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0401

Gnomad AMI

AF:

0.240

Gnomad AMR

AF:

0.0820

Gnomad ASJ

AF:

0.0867

Gnomad EAS

AF:

0.0300

Gnomad SAS

AF:

0.0707

Gnomad FIN

AF:

0.138

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0994

Gnomad OTH

AF:

0.0833

GnomAD3 exomes

AF:

0.0846

AC:

13485

AN:

159360

Hom.:

656

AF XY:

0.0854

AC XY:

7187

AN XY:

84148

show subpopulations

Gnomad AFR exome

AF:

0.0382

Gnomad AMR exome

AF:

0.0707

Gnomad ASJ exome

AF:

0.0851

Gnomad EAS exome

AF:

0.0296

Gnomad SAS exome

AF:

0.0764

Gnomad FIN exome

AF:

0.127

Gnomad NFE exome

AF:

0.0979

Gnomad OTH exome

AF:

0.0999

GnomAD4 exome

AF:

0.0965

AC:

134933

AN:

1398232

Hom.:

6881

Cov.:

AF XY:

0.0959

AC XY:

66208

AN XY:

690064

show subpopulations

Gnomad4 AFR exome

AF:

0.0402

Gnomad4 AMR exome

AF:

0.0715

Gnomad4 ASJ exome

AF:

0.0864

Gnomad4 EAS exome

AF:

0.0385

Gnomad4 SAS exome

AF:

0.0777

Gnomad4 FIN exome

AF:

0.129

Gnomad4 NFE exome

AF:

0.101

Gnomad4 OTH exome

AF:

0.0904

GnomAD4 genome

AF:

0.0813

AC:

12351

AN:

152006

Hom.:

608

Cov.:

AF XY:

0.0821

AC XY:

6097

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.0400

Gnomad4 AMR

AF:

0.0821

Gnomad4 ASJ

AF:

0.0867

Gnomad4 EAS

AF:

0.0304

Gnomad4 SAS

AF:

0.0727

Gnomad4 FIN

AF:

0.138

Gnomad4 NFE

AF:

0.0994

Gnomad4 OTH

AF:

0.0825

Alfa

AF:

0.0728

Hom.:

165

Bravo

AF:

0.0768

Asia WGS

AF:

0.0510

AC:

177

AN:

3476

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	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

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, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 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

-0.82

CADD

Benign

0.20

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.0060

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