2-190650716-A-T

Position:

• chr2-190650716-A-T

Variant summary

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

The NM_005966.4(NAB1):​c.-197+734A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 152,052 control chromosomes in the GnomAD database, including 15,928 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 0.45 (15928 hom., cov: 32)
• Consequence: NAB1 NM_005966.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAB1	NM_005966.4	c.-197+734A>T		intron_variant		ENST00000337386.10	NP_005957.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAB1	ENST00000337386.10	c.-197+734A>T		intron_variant		1	NM_005966.4	ENSP00000336894.5

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68977 AN: 151934 Hom.: 15910 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.454 AC: 69029 AN: 152052 Hom.: 15928 Cov.: 32 AF XY: 0.449 AC XY: 33347 AN XY: 74338

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.493

Gnomad4 OTH AF: 0.459

Alfa AF: 0.468 Hom.: 2119

Bravo AF: 0.449

Asia WGS AF: 0.395 AC: 1371 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.91

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: rs1023568; hg19: chr2-191515442;