rs6572697

Variant names:

• chr14-50793083-G-A
• rs6572697
• NM_020921.4:c.266-202C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020921.4(NIN):​c.266-202C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,060 control chromosomes in the GnomAD database, including 2,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2365 hom., cov: 31)
• Consequence: NIN NM_020921.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.536
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 14-50793083-G-A is Benign according to our data. Variant chr14-50793083-G-A is described in ClinVar as Benign. ClinVar VariationId is 1174330.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIN	NM_020921.4	c.266-202C>T		intron_variant	Intron 4 of 30	ENST00000530997.7	NP_065972.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIN	ENST00000530997.7	c.266-202C>T		intron_variant	Intron 4 of 30	5	NM_020921.4	ENSP00000436092.2

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25190 AN: 151942 Hom.: 2366 Cov.: 31

Gnomad AFR AF: 0.0864

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.166 AC: 25203 AN: 152060 Hom.: 2365 Cov.: 31 AF XY: 0.166 AC XY: 12313 AN XY: 74316

African (AFR) AF: 0.0865 AC: 3592 AN: 41524

American (AMR) AF: 0.192 AC: 2928 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 834 AN: 3466

East Asian (EAS) AF: 0.157 AC: 812 AN: 5158

South Asian (SAS) AF: 0.193 AC: 929 AN: 4814

European-Finnish (FIN) AF: 0.194 AC: 2043 AN: 10544

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13416 AN: 67978

Other (OTH) AF: 0.185 AC: 390 AN: 2112

Alfa AF: 0.159 Hom.: 395

Bravo AF: 0.163

Asia WGS AF: 0.166 AC: 574 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.62
PhyloP100		-0.54
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: rs6572697; hg19: chr14-51259801;