Genetic Variant DYNC1I1:c.224-142_224-140dupTTT (chr7-95813093-C-CTTT) – 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.224-142_224-140dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,112,896 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0013 ( 3 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: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 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.224-142_224-140dupTTT	intron	N/A	NP_001129028.1	O14576-2
DYNC1I1	NM_004411.5		c.224-91_224-89dupTTT	intron	N/A	NP_004402.1	O14576-1
DYNC1I1	NM_001278421.2		c.224-91_224-89dupTTT	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_224-153insTTT	intron	N/A	ENSP00000392337.2	O14576-2
DYNC1I1	ENST00000324972.10	TSL:1	c.224-103_224-102insTTT	intron	N/A	ENSP00000320130.6	O14576-1
DYNC1I1	ENST00000457059.2	TSL:1	c.224-154_224-153insTTT	intron	N/A	ENSP00000412444.1	O14576-2

Frequencies

GnomAD3 genomes

AF:

0.000392

AC:

AN:

140300

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000551

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000144

Gnomad ASJ

AF:

0.000591

Gnomad EAS

AF:

0.000620

Gnomad SAS

AF:

0.000221

Gnomad FIN

AF:

0.000141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00134

AC:

1299

AN:

972596

Hom.:

AF XY:

0.00146

AC XY:

708

AN XY:

483964

show subpopulations

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

African (AFR)

AF:

0.00742

AC:

139

AN:

18724

American (AMR)

AF:

0.00241

AC:

AN:

17426

Ashkenazi Jewish (ASJ)

AF:

0.00125

AC:

AN:

16864

East Asian (EAS)

AF:

0.00204

AC:

AN:

26484

South Asian (SAS)

AF:

0.00280

AC:

138

AN:

49322

European-Finnish (FIN)

AF:

0.00161

AC:

AN:

30434

Middle Eastern (MID)

AF:

0.00136

AC:

AN:

2944

European-Non Finnish (NFE)

AF:

0.00101

AC:

776

AN:

770052

Other (OTH)

AF:

0.00188

AC:

AN:

40346

⚠️ 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: 0.353

Heterozygous variant carriers

152

229

305

381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

104

130

<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:

0.000392

AC:

AN:

140300

Hom.:

Cov.:

AF XY:

0.000326

AC XY:

AN XY:

67524

show subpopulations

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

African (AFR)

AF:

0.000551

AC:

AN:

38088

American (AMR)

AF:

0.000144

AC:

AN:

13878

Ashkenazi Jewish (ASJ)

AF:

0.000591

AC:

AN:

3382

East Asian (EAS)

AF:

0.000620

AC:

AN:

4840

South Asian (SAS)

AF:

0.000221

AC:

AN:

4522

European-Finnish (FIN)

AF:

0.000141

AC:

AN:

7086

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000382

AC:

AN:

65396

Other (OTH)

AF:

0.00

AC:

AN:

1922

⚠️ 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: 0.323

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

Alfa

AF:

0.00

Hom.:

272

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

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7-95813093-CTTTTT-CTTTTTTTT

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