Variant 7-95813198-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000324972.10(DYNC1I1):c.226C>G(p.Gln76Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00241 in 1,611,400 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0040 ( 16 hom., cov: 30)

Exomes 𝑓: 0.0022 ( 69 hom. )

Consequence

DYNC1I1
ENST00000324972.10 missense, splice_region

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 4.73

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004395187).

BP6

Variant 7-95813198-C-G is Benign according to our data. Variant chr7-95813198-C-G is described in ClinVar as [Benign]. Clinvar id is 730484.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYNC1I1	NM_001135556.2 linkuse as main transcript	c.224-49C>G		intron_variant		ENST00000447467.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYNC1I1	ENST00000447467.6 linkuse as main transcript	c.224-49C>G		intron_variant		1	NM_001135556.2	P3	O14576-2

Frequencies

GnomAD3 genomes

AF:

0.00401

AC:

604

AN:

150558

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000734

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000662

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00312

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0455

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00149

Gnomad OTH

AF:

0.00193

GnomAD3 exomes

AF:

0.00497

AC:

1245

AN:

250440

Hom.:

AF XY:

0.00465

AC XY:

629

AN XY:

135334

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00538

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0394

Gnomad NFE exome

AF:

0.00253

Gnomad OTH exome

AF:

0.00671

GnomAD4 exome

AF:

0.00224

AC:

3275

AN:

1460746

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

1613

AN XY:

726694

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00510

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.0403

Gnomad4 NFE exome

AF:

0.000687

Gnomad4 OTH exome

AF:

0.00310

GnomAD4 genome

AF:

0.00402

AC:

605

AN:

150654

Hom.:

Cov.:

AF XY:

0.00567

AC XY:

417

AN XY:

73492

show subpopulations

Gnomad4 AFR

AF:

0.0000732

Gnomad4 AMR

AF:

0.0000661

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00333

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0455

Gnomad4 NFE

AF:

0.00149

Gnomad4 OTH

AF:

0.00191

Alfa

AF:

0.00161

Hom.:

Bravo

AF:

0.000669

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.00506

AC:

614

Asia WGS

AF:

0.00982

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DYNC1I1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 24, 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). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 17, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Benign

0.51

DEOGEN2

Benign

0.085

T;.

Eigen

Benign

-0.20

Eigen_PC

Benign

0.015

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.68

T;T

MetaRNN

Benign

0.0044

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.2

L;L

MutationTaster

Benign

0.90

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.16

N;N

REVEL

Benign

0.15

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0030

B;.

Vest4

0.49

MVP

0.68

MPC

0.59

ClinPred

0.020

GERP RS

4.8

Varity_R

0.15

gMVP

0.073

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

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