chr14-50725777-G-A

Position:

• chr14-50725777-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020921.4(NIN):​c.6192+176C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00678 in 1,121,942 control chromosomes in the GnomAD database, including 398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (243 hom., cov: 31)
  • Exomes 𝑓: 0.0031 (155 hom.)
• Consequence: NIN NM_020921.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.640

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 14-50725777-G-A is Benign according to our data. Variant chr14-50725777-G-A is described in ClinVar as [Benign]. Clinvar id is 1274581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIN	NM_020921.4	c.6192+176C>T		intron_variant		ENST00000530997.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIN	ENST00000530997.7	c.6192+176C>T		intron_variant		5	NM_020921.4	P2

Frequencies

GnomAD3 genomes AF: 0.0303 AC: 4603 AN: 152030 Hom.: 240 Cov.: 31

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.0187

GnomAD4 exome AF: 0.00308 AC: 2989 AN: 969794 Hom.: 155 Cov.: 12 AF XY: 0.00269 AC XY: 1308 AN XY: 487110

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.00561

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000143

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000193

Gnomad4 OTH exome AF: 0.00718

GnomAD4 genome AF: 0.0303 AC: 4615 AN: 152148 Hom.: 243 Cov.: 31 AF XY: 0.0295 AC XY: 2191 AN XY: 74386

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.0107

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.00603 Hom.: 6

Bravo AF: 0.0341

Asia WGS AF: 0.00491 AC: 17 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.22
DANN	Benign	0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs75764688; hg19: chr14-51192495;