Genetic Variant DYNC1I1:c.224-140dupT (chr7-95813093-C-CT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001135556.2(DYNC1I1):c.224-140dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,097,144 control chromosomes in the GnomAD database, including 20,068 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.41 ( 11975 hom., cov: 0)

Exomes 𝑓: 0.32 ( 8093 hom. )

Consequence

DYNC1I1
NM_001135556.2 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.361

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 7-95813093-C-CT is Benign according to our data. Variant chr7-95813093-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1285939.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135556.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DYNC1I1	NM_001135556.2	MANE Select	c.224-140dupT	intron	N/A	NP_001129028.1	O14576-2
DYNC1I1	NM_004411.5		c.224-89dupT	intron	N/A	NP_004402.1	O14576-1
DYNC1I1	NM_001278421.2		c.224-89dupT	intron	N/A	NP_001265350.1	O14576-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DYNC1I1	ENST00000447467.6	TSL:1 MANE Select	c.224-154_224-153insT	intron	N/A	ENSP00000392337.2	O14576-2
DYNC1I1	ENST00000324972.10	TSL:1	c.224-103_224-102insT	intron	N/A	ENSP00000320130.6	O14576-1
DYNC1I1	ENST00000457059.2	TSL:1	c.224-154_224-153insT	intron	N/A	ENSP00000412444.1	O14576-2

Frequencies

GnomAD3 genomes

AF:

0.410

AC:

57465

AN:

140216

Hom.:

11956

Cov.:

show subpopulations

Gnomad AFR

AF:

0.474

Gnomad AMI

AF:

0.257

Gnomad AMR

AF:

0.461

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.566

Gnomad SAS

AF:

0.408

Gnomad FIN

AF:

0.362

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.362

Gnomad OTH

AF:

0.402

GnomAD4 exome

AF:

0.317

AC:

303736

AN:

956916

Hom.:

8093

AF XY:

0.314

AC XY:

149570

AN XY:

476124

show subpopulations

African (AFR)

AF:

0.351

AC:

6529

AN:

18584

American (AMR)

AF:

0.332

AC:

5727

AN:

17246

Ashkenazi Jewish (ASJ)

AF:

0.284

AC:

4699

AN:

16556

East Asian (EAS)

AF:

0.356

AC:

9254

AN:

26028

South Asian (SAS)

AF:

0.253

AC:

12378

AN:

49006

European-Finnish (FIN)

AF:

0.297

AC:

8884

AN:

29946

Middle Eastern (MID)

AF:

0.281

AC:

811

AN:

2886

European-Non Finnish (NFE)

AF:

0.321

AC:

242868

AN:

756956

Other (OTH)

AF:

0.317

AC:

12586

AN:

39708

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

8887

17773

26660

35546

44433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9644

19288

28932

38576

48220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.410

AC:

57497

AN:

140228

Hom.:

11975

Cov.:

AF XY:

0.411

AC XY:

27735

AN XY:

67496

show subpopulations

African (AFR)

AF:

0.474

AC:

18068

AN:

38126

American (AMR)

AF:

0.461

AC:

6395

AN:

13860

Ashkenazi Jewish (ASJ)

AF:

0.343

AC:

1161

AN:

3382

East Asian (EAS)

AF:

0.566

AC:

2730

AN:

4824

South Asian (SAS)

AF:

0.409

AC:

1836

AN:

4488

European-Finnish (FIN)

AF:

0.362

AC:

2555

AN:

7064

Middle Eastern (MID)

AF:

0.311

AC:

AN:

270

European-Non Finnish (NFE)

AF:

0.362

AC:

23646

AN:

65384

Other (OTH)

AF:

0.409

AC:

793

AN:

1938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

1510

3020

4529

6039

7549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

548

1096

1644

2192

2740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.172

Hom.:

272

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over