12-57091245-C-T

Variant names:

• chr12-57091245-C-T
• rs151285788
• NM_005967.4:c.204C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_005967.4(NAB2):​c.204C>T​(p.Asp68Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000957 in 1,601,590 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00097 (2 hom.)
• Consequence: NAB2 NM_005967.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.111
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 12-57091245-C-T is Benign according to our data. Variant chr12-57091245-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2643108.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.111 with no splicing effect.
• BS2: High AC in GnomAd4 at 130 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005967.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAB2	NM_005967.4	MANE Select	c.204C>T	p.Asp68Asp	synonymous	Exon 2 of 7	NP_005958.1	Q15742-1
	NAB2	NM_001330305.2		c.204C>T	p.Asp68Asp	synonymous	Exon 2 of 6	NP_001317234.1	Q15742-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAB2	ENST00000300131.8	TSL:1 MANE Select	c.204C>T	p.Asp68Asp	synonymous	Exon 2 of 7	ENSP00000300131.3	Q15742-1
	NAB2	ENST00000953388.1		c.204C>T	p.Asp68Asp	synonymous	Exon 2 of 7	ENSP00000623447.1
	NAB2	ENST00000862010.1		c.204C>T	p.Asp68Asp	synonymous	Exon 2 of 7	ENSP00000532069.1

Frequencies

GnomAD3 genomes AF: 0.000855 AC: 130 AN: 152118 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00110

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000670 AC: 166 AN: 247794 AF XY: 0.000576

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.000409

Gnomad ASJ exome AF: 0.000416

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000468

Gnomad NFE exome AF: 0.00120

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.000968 AC: 1403 AN: 1449354 Hom.: 2 Cov.: 31 AF XY: 0.000939 AC XY: 675 AN XY: 718586

African (AFR) AF: 0.000211 AC: 7 AN: 33248

American (AMR) AF: 0.000677 AC: 30 AN: 44320

Ashkenazi Jewish (ASJ) AF: 0.000429 AC: 11 AN: 25652

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39382

South Asian (SAS) AF: 0.0000234 AC: 2 AN: 85438

European-Finnish (FIN) AF: 0.0000376 AC: 2 AN: 53138

Middle Eastern (MID) AF: 0.000699 AC: 4 AN: 5724

European-Non Finnish (NFE) AF: 0.00118 AC: 1302 AN: 1102698

Other (OTH) AF: 0.000736 AC: 44 AN: 59754

GnomAD4 genome AF: 0.000854 AC: 130 AN: 152236 Hom.: 0 Cov.: 32 AF XY: 0.000792 AC XY: 59 AN XY: 74454

African (AFR) AF: 0.000337 AC: 14 AN: 41536

American (AMR) AF: 0.00209 AC: 32 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00110 AC: 75 AN: 68014

Other (OTH) AF: 0.00237 AC: 5 AN: 2110

Alfa AF: 0.000811 Hom.: 0

Bravo AF: 0.000990

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.6
DANN	Benign	0.91
PhyloP100		-0.11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=95/5	polymorphism

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: rs151285788; hg19: chr12-57485028;