14-50803549-G-C

Variant names:

• chr14-50803549-G-C
• rs9788504
• NM_020921.4:c.265+3188C>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.265+3188C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,926 control chromosomes in the GnomAD database, including 20,853 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 0.51 (20853 hom., cov: 31)
• Consequence: NIN NM_020921.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.606 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIN	NM_020921.4	MANE Select	c.265+3188C>G		intron	N/A	NP_065972.4
	NIN	NM_182946.2		c.265+3188C>G		intron	N/A	NP_891991.2
	NIN	NM_182944.3		c.265+3188C>G		intron	N/A	NP_891989.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIN	ENST00000530997.7	TSL:5 MANE Select	c.265+3188C>G		intron	N/A	ENSP00000436092.2
	NIN	ENST00000382041.7	TSL:1	c.265+3188C>G		intron	N/A	ENSP00000371472.3
	NIN	ENST00000382043.8	TSL:1	c.265+3188C>G		intron	N/A	ENSP00000371474.4

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77880 AN: 151808 Hom.: 20848 Cov.: 31

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.513 AC: 77912 AN: 151926 Hom.: 20853 Cov.: 31 AF XY: 0.511 AC XY: 37913 AN XY: 74244

African (AFR) AF: 0.375 AC: 15514 AN: 41410

American (AMR) AF: 0.412 AC: 6296 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2182 AN: 3468

East Asian (EAS) AF: 0.557 AC: 2868 AN: 5152

South Asian (SAS) AF: 0.624 AC: 3005 AN: 4814

European-Finnish (FIN) AF: 0.534 AC: 5646 AN: 10564

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40488 AN: 67934

Other (OTH) AF: 0.546 AC: 1150 AN: 2108

Alfa AF: 0.406 Hom.: 1165

Bravo AF: 0.495

Asia WGS AF: 0.581 AC: 2023 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.59
PhyloP100		-0.21
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: rs9788504; hg19: chr14-51270267;