14-50750856-T-G

Variant names:

• chr14-50750856-T-G
• rs4901053
• NM_020921.4:c.4950+1662A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020921.4(NIN):​c.4950+1662A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 152,000 control chromosomes in the GnomAD database, including 19,935 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 (19935 hom., cov: 32)
• Consequence: NIN NM_020921.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.17
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 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.4950+1662A>C		intron	N/A	NP_065972.4
	NIN	NM_182946.2		c.4950+1662A>C		intron	N/A	NP_891991.2
	NIN	NM_182944.3		c.4950+1662A>C		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.4950+1662A>C		intron	N/A	ENSP00000436092.2
	NIN	ENST00000382041.7	TSL:1	c.4950+1662A>C		intron	N/A	ENSP00000371472.3
	NIN	ENST00000382043.8	TSL:1	c.2811+1662A>C		intron	N/A	ENSP00000371474.4

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76897 AN: 151880 Hom.: 19907 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.506 AC: 76961 AN: 152000 Hom.: 19935 Cov.: 32 AF XY: 0.504 AC XY: 37420 AN XY: 74296

African (AFR) AF: 0.586 AC: 24281 AN: 41444

American (AMR) AF: 0.566 AC: 8639 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1903 AN: 3464

East Asian (EAS) AF: 0.569 AC: 2936 AN: 5164

South Asian (SAS) AF: 0.320 AC: 1544 AN: 4828

European-Finnish (FIN) AF: 0.414 AC: 4381 AN: 10570

Middle Eastern (MID) AF: 0.514 AC: 150 AN: 292

European-Non Finnish (NFE) AF: 0.466 AC: 31655 AN: 67946

Other (OTH) AF: 0.508 AC: 1071 AN: 2108

Alfa AF: 0.449 Hom.: 8209

Bravo AF: 0.527

Asia WGS AF: 0.445 AC: 1551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.64
DANN	Benign	0.33
PhyloP100		-3.2
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: rs4901053; hg19: chr14-51217574;