chr14-50759006-C-T

Position:

• chr14-50759006-C-T

Variant summary

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

The NM_020921.4(NIN):​c.2400-376G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,114 control chromosomes in the GnomAD database, including 6,776 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 0.28 (6776 hom., cov: 33)
• Consequence: NIN NM_020921.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIN	NM_020921.4	c.2400-376G>A		intron_variant		ENST00000530997.7	NP_065972.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NIN	ENST00000530997.7	c.2400-376G>A		intron_variant		5	NM_020921.4	ENSP00000436092	P2

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42206 AN: 151996 Hom.: 6769 Cov.: 33

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.278 AC: 42218 AN: 152114 Hom.: 6776 Cov.: 33 AF XY: 0.284 AC XY: 21142 AN XY: 74344

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.284

Alfa AF: 0.298 Hom.: 4168

Bravo AF: 0.280

Asia WGS AF: 0.354 AC: 1231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.8
DANN	Benign	0.69

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: rs10483610; hg19: chr14-51225724;