14-50812661-T-C

Variant names:

• chr14-50812661-T-C
• rs12883458
• NM_020921.4:c.184-5843A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020921.4(NIN):​c.184-5843A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0879 in 152,266 control chromosomes in the GnomAD database, including 723 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 0.088 (723 hom., cov: 32)
• Consequence: NIN NM_020921.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.518
• Publications: 7 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIN	NM_020921.4	c.184-5843A>G		intron_variant	Intron 3 of 30	ENST00000530997.7	NP_065972.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIN	ENST00000530997.7	c.184-5843A>G		intron_variant	Intron 3 of 30	5	NM_020921.4	ENSP00000436092.2

Frequencies

GnomAD3 genomes AF: 0.0879 AC: 13380 AN: 152148 Hom.: 724 Cov.: 32

Gnomad AFR AF: 0.0315

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0969

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

GnomAD4 genome AF: 0.0879 AC: 13385 AN: 152266 Hom.: 723 Cov.: 32 AF XY: 0.0892 AC XY: 6642 AN XY: 74452

African (AFR) AF: 0.0315 AC: 1308 AN: 41570

American (AMR) AF: 0.138 AC: 2112 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 455 AN: 3470

East Asian (EAS) AF: 0.101 AC: 525 AN: 5182

South Asian (SAS) AF: 0.103 AC: 499 AN: 4828

European-Finnish (FIN) AF: 0.121 AC: 1288 AN: 10606

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6877 AN: 68006

Other (OTH) AF: 0.0988 AC: 209 AN: 2116

Alfa AF: 0.0956 Hom.: 1668

Bravo AF: 0.0873

Asia WGS AF: 0.107 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	15
DANN	Benign	0.68
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12883458; hg19: chr14-51279379;