rs8009874

Positions:

• chr14-50806106-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020921.4(NIN):​c.265+631A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0805 in 152,312 control chromosomes in the GnomAD database, including 627 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 0.081 (627 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NIN NM_020921.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.460

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIN	NM_020921.4	c.265+631A>G		intron_variant		ENST00000530997.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIN	ENST00000530997.7	c.265+631A>G		intron_variant		5	NM_020921.4	P2

Frequencies

GnomAD3 genomes AF: 0.0806 AC: 12262 AN: 152194 Hom.: 629 Cov.: 32

Gnomad AFR AF: 0.0199

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0925

Gnomad OTH AF: 0.0913

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0805 AC: 12262 AN: 152312 Hom.: 627 Cov.: 32 AF XY: 0.0828 AC XY: 6163 AN XY: 74460

Gnomad4 AFR AF: 0.0198

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.0925

Gnomad4 OTH AF: 0.0932

Alfa AF: 0.0792 Hom.: 74

Bravo AF: 0.0791

Asia WGS AF: 0.109 AC: 378 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.0
DANN	Benign	0.81

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

LitVar

Other links and lift over

dbSNP: rs8009874; hg19: chr14-51272824;