chr14-50759006-C-T

Variant names:

• chr14-50759006-C-T
• rs10483610
• NM_020921.4:c.2400-376G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.8).
• 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 rank	MANE	Protein	UniProt
NIN	NM_020921.4	c.2400-376G>A		intron_variant	Intron 17 of 30	ENST00000530997.7	NP_065972.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIN	ENST00000530997.7	c.2400-376G>A		intron_variant	Intron 17 of 30	5	NM_020921.4	ENSP00000436092.2

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

African (AFR) AF: 0.128 AC: 5330 AN: 41526

American (AMR) AF: 0.400 AC: 6108 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1290 AN: 3464

East Asian (EAS) AF: 0.514 AC: 2661 AN: 5178

South Asian (SAS) AF: 0.314 AC: 1511 AN: 4818

European-Finnish (FIN) AF: 0.317 AC: 3345 AN: 10546

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21097 AN: 67990

Other (OTH) AF: 0.284 AC: 600 AN: 2110

Alfa AF: 0.301 Hom.: 6023

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
PhyloP100		0.16
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: rs10483610; hg19: chr14-51225724;