11-17329656-A-G

Variant names:

• chr11-17329656-A-G
• rs10832763
• NM_005013.4:c.1003-471A>G

Variant summary

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

The NM_005013.4(NUCB2):​c.1003-471A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,090 control chromosomes in the GnomAD database, including 7,586 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 0.30 (7586 hom., cov: 32)
• Consequence: NUCB2 NM_005013.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• Publications: 7 publications found

Genes affected

NUCB2 (HGNC:8044): (nucleobindin 2) This gene encodes a protein with a suggested role in calcium level maintenance, eating regulation in the hypothalamus, and release of tumor necrosis factor from vascular endothelial cells. This protein binds calcium and has EF-folding domains. [provided by RefSeq, Oct 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005013.4. 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
	NUCB2	NM_005013.4	MANE Select	c.1003-471A>G		intron	N/A	NP_005004.1
	NUCB2	NM_001352661.2		c.1006-471A>G		intron	N/A	NP_001339590.1
	NUCB2	NM_001352663.2		c.1006-471A>G		intron	N/A	NP_001339592.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUCB2	ENST00000529010.6	TSL:1 MANE Select	c.1003-471A>G		intron	N/A	ENSP00000436455.1
	NUCB2	ENST00000646648.1		n.*315-471A>G		intron	N/A	ENSP00000495210.1
	NUCB2	ENST00000909741.1		c.1057-471A>G		intron	N/A	ENSP00000579800.1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45530 AN: 151970 Hom.: 7586 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.299 AC: 45551 AN: 152090 Hom.: 7586 Cov.: 32 AF XY: 0.303 AC XY: 22541 AN XY: 74326

African (AFR) AF: 0.178 AC: 7367 AN: 41504

American (AMR) AF: 0.226 AC: 3457 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1168 AN: 3472

East Asian (EAS) AF: 0.517 AC: 2665 AN: 5152

South Asian (SAS) AF: 0.283 AC: 1363 AN: 4820

European-Finnish (FIN) AF: 0.429 AC: 4541 AN: 10578

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24054 AN: 67962

Other (OTH) AF: 0.291 AC: 613 AN: 2108

Alfa AF: 0.210 Hom.: 556

Bravo AF: 0.278

Asia WGS AF: 0.359 AC: 1247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.46
DANN	Benign	0.14
PhyloP100		-1.6
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: rs10832763; hg19: chr11-17351203;