Genetic Variant DYNC1I1:c.224-142_224-140delTTT (chr7-95813093-CTTT-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001135556.2(DYNC1I1):c.224-142_224-140delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000166 in 1,113,050 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000071 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

DYNC1I1
NM_001135556.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.756

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.224-142_224-140delTTT	intron	N/A	NP_001129028.1	O14576-2
DYNC1I1	NM_004411.5		c.224-91_224-89delTTT	intron	N/A	NP_004402.1	O14576-1
DYNC1I1	NM_001278421.2		c.224-91_224-89delTTT	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.224-153_224-151delTTT	intron	N/A	ENSP00000392337.2	O14576-2
DYNC1I1	ENST00000324972.10	TSL:1	c.224-102_224-100delTTT	intron	N/A	ENSP00000320130.6	O14576-1
DYNC1I1	ENST00000457059.2	TSL:1	c.224-153_224-151delTTT	intron	N/A	ENSP00000412444.1	O14576-2

Frequencies

GnomAD3 genomes

AF:

0.00000712

AC:

AN:

140372

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000189

AC:

184

AN:

972678

Hom.:

AF XY:

0.000192

AC XY:

AN XY:

484000

show subpopulations

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

African (AFR)

AF:

0.000213

AC:

AN:

18778

American (AMR)

AF:

0.0000573

AC:

AN:

17450

Ashkenazi Jewish (ASJ)

AF:

0.000178

AC:

AN:

16824

East Asian (EAS)

AF:

0.000302

AC:

AN:

26514

South Asian (SAS)

AF:

0.000284

AC:

AN:

49272

European-Finnish (FIN)

AF:

0.000329

AC:

AN:

30430

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2948

European-Non Finnish (NFE)

AF:

0.000173

AC:

133

AN:

770102

Other (OTH)

AF:

0.000273

AC:

AN:

40360

⚠️ 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: 0.240

Heterozygous variant carriers

118

148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.00000712

AC:

AN:

140372

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

67554

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

38112

American (AMR)

AF:

0.00

AC:

AN:

13880

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3382

East Asian (EAS)

AF:

0.00

AC:

AN:

4846

South Asian (SAS)

AF:

0.00

AC:

AN:

4522

European-Finnish (FIN)

AF:

0.000141

AC:

AN:

7084

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65436

Other (OTH)

AF:

0.00

AC:

AN:

1924

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 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: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.76

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over