rs10490539

Variant names:

• chr2-190688696-T-C
• rs10490539
• NM_005966.4:c.1375+1379T>C

Variant summary

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

The NM_005966.4(NAB1):​c.1375+1379T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,240 control chromosomes in the GnomAD database, including 1,530 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 0.10 (1530 hom., cov: 32)
• Consequence: NAB1 NM_005966.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410
• Publications: 1 publications found

Genes affected

NAB1 (HGNC:7626): (NGFI-A binding protein 1) Predicted to enable transcription coregulator activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to act upstream of or within endochondral ossification; nervous system development; and regulation of epidermis development. Predicted to be located in nucleoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000228509 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAB1	NM_005966.4	c.1375+1379T>C		intron_variant	Intron 9 of 9	ENST00000337386.10	NP_005957.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAB1	ENST00000337386.10	c.1375+1379T>C		intron_variant	Intron 9 of 9	1	NM_005966.4	ENSP00000336894.5

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15892 AN: 152122 Hom.: 1511 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0750

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0275

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.00895

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0444

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.105 AC: 15951 AN: 152240 Hom.: 1530 Cov.: 32 AF XY: 0.102 AC XY: 7577 AN XY: 74458

African (AFR) AF: 0.247 AC: 10230 AN: 41488

American (AMR) AF: 0.0748 AC: 1145 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 497 AN: 3470

East Asian (EAS) AF: 0.0276 AC: 143 AN: 5190

South Asian (SAS) AF: 0.106 AC: 511 AN: 4828

European-Finnish (FIN) AF: 0.00895 AC: 95 AN: 10614

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0444 AC: 3022 AN: 68026

Other (OTH) AF: 0.118 AC: 249 AN: 2110

Alfa AF: 0.104 Hom.: 233

Bravo AF: 0.114

Asia WGS AF: 0.0560 AC: 196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.40
PhyloP100		-0.041
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: rs10490539; hg19: chr2-191553422;