Genetic Variant DYNC1I1:c.224-140_224-139insTTTTTTTTTTTTTTTTTTTTTT (chr7-95813093-C-CTTTTTTTTTTTTTTTTTTTTTT) – 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.224-140_224-139insTTTTTTTTTTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000538 in 1,114,300 control chromosomes in the GnomAD database, including 1 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000028 ( 1 hom., cov: 0)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DYNC1I1
NM_001135556.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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:

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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.224-140_224-139insTTTTTTTTTTTTTTTTTTTTTT	intron	N/A	NP_001129028.1	O14576-2
DYNC1I1	NM_004411.5		c.224-89_224-88insTTTTTTTTTTTTTTTTTTTTTT	intron	N/A	NP_004402.1	O14576-1
DYNC1I1	NM_001278421.2		c.224-89_224-88insTTTTTTTTTTTTTTTTTTTTTT	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_224-153insTTTTTTTTTTTTTTTTTTTTTT	intron	N/A	ENSP00000392337.2	O14576-2
DYNC1I1	ENST00000324972.10	TSL:1	c.224-103_224-102insTTTTTTTTTTTTTTTTTTTTTT	intron	N/A	ENSP00000320130.6	O14576-1
DYNC1I1	ENST00000457059.2	TSL:1	c.224-154_224-153insTTTTTTTTTTTTTTTTTTTTTT	intron	N/A	ENSP00000412444.1	O14576-2

Frequencies

GnomAD3 genomes

AF:

0.0000285

AC:

AN:

140374

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000611

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

973926

Hom.:

AF XY:

0.00000206

AC XY:

AN XY:

484632

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18796

American (AMR)

AF:

0.00

AC:

AN:

17456

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16878

East Asian (EAS)

AF:

0.0000377

AC:

AN:

26528

South Asian (SAS)

AF:

0.00

AC:

AN:

49364

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30472

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2948

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

771072

Other (OTH)

AF:

0.0000247

AC:

AN:

40412

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.750

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000285

AC:

AN:

140374

Hom.:

Cov.:

AF XY:

0.0000148

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:

0.00

AC:

AN:

7086

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000611

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 = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.36

Splicing

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.

7-95813093-CTTTTT-CTTTTTTTTTTTTTTTTTTTTTTTTTTT

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