12-57094510-A-T

Position:

• chr12-57094510-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005967.4(NAB2):​c.1469-102A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0841 in 913,236 control chromosomes in the GnomAD database, including 3,794 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 0.070 (536 hom., cov: 32)
  • Exomes 𝑓: 0.087 (3258 hom.)
• Consequence: NAB2 NM_005967.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.393

Genes affected

NAB2 (HGNC:7627): (NGFI-A binding protein 2) This gene encodes a member of the family of NGFI-A binding (NAB) proteins, which function in the nucleus to repress transcription induced by some members of the EGR (early growth response) family of transactivators. NAB proteins can homo- or hetero-multimerize with other EGR or NAB proteins through a conserved N-terminal domain, and repress transcription through two partially redundant C-terminal domains. Transcriptional repression by the encoded protein is mediated in part by interactions with the nucleosome remodeling and deactylase (NuRD) complex. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAB2	NM_005967.4	c.1469-102A>T		intron_variant		ENST00000300131.8	NP_005958.1
NAB2	NM_001330305.2	c.1277-102A>T		intron_variant			NP_001317234.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAB2	ENST00000300131.8	c.1469-102A>T		intron_variant		1	NM_005967.4	ENSP00000300131.3
NAB2	ENST00000342556.6	c.1277-102A>T		intron_variant		5		ENSP00000341491.6

Frequencies

GnomAD3 genomes AF: 0.0705 AC: 10717 AN: 152012 Hom.: 535 Cov.: 32

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0794

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0336

Gnomad FIN AF: 0.0688

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.0869 AC: 66133 AN: 761106 Hom.: 3258 AF XY: 0.0851 AC XY: 33872 AN XY: 398092

Gnomad4 AFR exome AF: 0.0195

Gnomad4 AMR exome AF: 0.0689

Gnomad4 ASJ exome AF: 0.134

Gnomad4 EAS exome AF: 0.000182

Gnomad4 SAS exome AF: 0.0337

Gnomad4 FIN exome AF: 0.0767

Gnomad4 NFE exome AF: 0.101

Gnomad4 OTH exome AF: 0.0951

GnomAD4 genome AF: 0.0704 AC: 10714 AN: 152130 Hom.: 536 Cov.: 32 AF XY: 0.0682 AC XY: 5068 AN XY: 74362

Gnomad4 AFR AF: 0.0180

Gnomad4 AMR AF: 0.0793

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0338

Gnomad4 FIN AF: 0.0688

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0857 Hom.: 80

Bravo AF: 0.0718

Asia WGS AF: 0.0150 AC: 55 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3024979; hg19: chr12-57488293; COSMIC: COSV100272550; COSMIC: COSV100272550;