rs10490539

Positions:

• chr2-190688696-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NAB1	NM_005966.4	c.1375+1379T>C		intron_variant		ENST00000337386.10	NP_005957.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAB1	ENST00000337386.10	c.1375+1379T>C		intron_variant		1	NM_005966.4	ENSP00000336894	P4
	ENST00000676095.2	n.517+1654A>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.0748

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.0276

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.00895

Gnomad4 NFE AF: 0.0444

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0995 Hom.: 204

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs10490539; hg19: chr2-191553422;