Genetic Variant DYNC1I1:c.314+56delA (chr7-95813378-TA-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001135556.2(DYNC1I1):c.314+56delA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0043 ( 3 hom., cov: 0)

Exomes 𝑓: 0.069 ( 0 hom. )

Consequence

DYNC1I1
NM_001135556.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.299

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

new If you want to explore the variant's impact on the transcript NM_001135556.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 3 gene

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.314+56delA	intron	N/A	NP_001129028.1	O14576-2
DYNC1I1	NM_004411.5		c.365+56delA	intron	N/A	NP_004402.1	O14576-1
DYNC1I1	NM_001278421.2		c.365+56delA	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.314+42delA	intron	N/A	ENSP00000392337.2	O14576-2
DYNC1I1	ENST00000324972.10	TSL:1	c.365+42delA	intron	N/A	ENSP00000320130.6	O14576-1
DYNC1I1	ENST00000457059.2	TSL:1	c.314+42delA	intron	N/A	ENSP00000412444.1	O14576-2

Frequencies

GnomAD3 genomes

AF:

0.00431

AC:

608

AN:

141000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0108

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00163

Gnomad ASJ

AF:

0.000302

Gnomad EAS

AF:

0.000827

Gnomad SAS

AF:

0.00588

Gnomad FIN

AF:

0.00317

Gnomad MID

AF:

0.0233

Gnomad NFE

AF:

0.00149

Gnomad OTH

AF:

0.00310

GnomAD2 exomes

AF:

0.119

AC:

12791

AN:

107330

AF XY:

0.126

show subpopulations

Gnomad AFR exome

AF:

0.0775

Gnomad AMR exome

AF:

0.0870

Gnomad ASJ exome

AF:

0.159

Gnomad EAS exome

AF:

0.0578

Gnomad FIN exome

AF:

0.104

Gnomad NFE exome

AF:

0.137

Gnomad OTH exome

AF:

0.122

GnomAD4 exome

AF:

0.0690

AC:

83476

AN:

1209938

Hom.:

Cov.:

AF XY:

0.0707

AC XY:

42375

AN XY:

599392

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0438

AC:

1163

AN:

26552

American (AMR)

AF:

0.0623

AC:

1506

AN:

24174

Ashkenazi Jewish (ASJ)

AF:

0.0881

AC:

1752

AN:

19876

East Asian (EAS)

AF:

0.0468

AC:

1599

AN:

34156

South Asian (SAS)

AF:

0.0849

AC:

5590

AN:

65872

European-Finnish (FIN)

AF:

0.0810

AC:

3210

AN:

39638

Middle Eastern (MID)

AF:

0.0640

AC:

294

AN:

4592

European-Non Finnish (NFE)

AF:

0.0687

AC:

64880

AN:

944898

Other (OTH)

AF:

0.0694

AC:

3482

AN:

50180

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.277

Heterozygous variant carriers

7356

14712

22068

29424

36780

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

2244

4488

6732

8976

11220

<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:

0.00433

AC:

611

AN:

141010

Hom.:

Cov.:

AF XY:

0.00472

AC XY:

321

AN XY:

68080

show subpopulations

African (AFR)

AF:

0.0109

AC:

424

AN:

38794

American (AMR)

AF:

0.00163

AC:

AN:

14130

Ashkenazi Jewish (ASJ)

AF:

0.000302

AC:

AN:

3310

East Asian (EAS)

AF:

0.000830

AC:

AN:

4822

South Asian (SAS)

AF:

0.00591

AC:

AN:

4402

European-Finnish (FIN)

AF:

0.00317

AC:

AN:

7882

Middle Eastern (MID)

AF:

0.0219

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.00149

AC:

AN:

64574

Other (OTH)

AF:

0.00308

AC:

AN:

1948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

102

128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000289

Hom.:

196

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.30

Mutation Taster

=100/0

polymorphism

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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7-95813378-TAAAAA-TAAAA

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