Genetic Variant NIN:c.184-2473A>T (chr14-50809291-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020921.4(NIN):c.184-2473A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,986 control chromosomes in the GnomAD database, including 8,025 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.31 ( 8025 hom., cov: 31)

Consequence

NIN
NM_020921.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.46

Publications

4 publications found

Variant links:

Genes affected

NIN (HGNC:14906): (ninein) This gene encodes one of the proteins important for centrosomal function. This protein is important for positioning and anchoring the microtubules minus-ends in epithelial cells. Localization of this protein to the centrosome requires three leucine zippers in the central coiled-coil domain. Multiple alternatively spliced transcript variants that encode different isoforms have been reported. [provided by RefSeq, Jul 2008]

NIN Gene-Disease associations (from GenCC):

Seckel syndrome 7
Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

NIN links:

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new If you want to explore the variant's impact on the transcript NM_020921.4, 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020921.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NIN	NM_020921.4	MANE Select	c.184-2473A>T	intron	N/A	NP_065972.4
NIN	NM_182946.2		c.184-2473A>T	intron	N/A	NP_891991.2	Q8N4C6-1
NIN	NM_182944.3		c.184-2473A>T	intron	N/A	NP_891989.3	C9J066

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NIN	ENST00000530997.7	TSL:5 MANE Select	c.184-2473A>T	intron	N/A	ENSP00000436092.2	Q8N4C6-7
NIN	ENST00000382041.7	TSL:1	c.184-2473A>T	intron	N/A	ENSP00000371472.3	Q8N4C6-1
NIN	ENST00000382043.8	TSL:1	c.184-2473A>T	intron	N/A	ENSP00000371474.4	Q8N4C6-11

Frequencies

GnomAD3 genomes

AF:

0.307

AC:

46602

AN:

151866

Hom.:

8016

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.338

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.420

Gnomad EAS

AF:

0.132

Gnomad SAS

AF:

0.366

Gnomad FIN

AF:

0.313

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.397

Gnomad OTH

AF:

0.319

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.307

AC:

46625

AN:

151986

Hom.:

8025

Cov.:

AF XY:

0.302

AC XY:

22427

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.186

AC:

7729

AN:

41458

American (AMR)

AF:

0.237

AC:

3613

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.420

AC:

1454

AN:

3464

East Asian (EAS)

AF:

0.132

AC:

682

AN:

5170

South Asian (SAS)

AF:

0.368

AC:

1770

AN:

4812

European-Finnish (FIN)

AF:

0.313

AC:

3301

AN:

10556

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.397

AC:

26978

AN:

67950

Other (OTH)

AF:

0.322

AC:

681

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1575

3151

4726

6302

7877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

474

948

1422

1896

2370

<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:

0.210

Hom.:

484

Bravo

AF:

0.293

Asia WGS

AF:

0.237

AC:

829

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0010

(source)

DANN

Benign

0.49

PhyloP100

-4.5

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

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

Publications

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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