NM_005013.4:c.-1+827T>G

Variant names:

• chr11-17283770-T-G
• rs214070
• NM_005013.4:c.-1+827T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005013.4(NUCB2):​c.-1+827T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: NUCB2 NM_005013.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138
• Publications: 5 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUCB2	NM_005013.4	MANE Select	c.-1+827T>G		intron	N/A	NP_005004.1
	NUCB2	NM_001352661.2		c.-208+827T>G		intron	N/A	NP_001339590.1
	NUCB2	NM_001352663.2		c.-124+827T>G		intron	N/A	NP_001339592.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUCB2	ENST00000529010.6	TSL:1 MANE Select	c.-1+827T>G		intron	N/A	ENSP00000436455.1
	NUCB2	ENST00000526120.5	TSL:1	c.-1+827T>G		intron	N/A	ENSP00000436215.1
	NUCB2	ENST00000533738.6	TSL:1	c.-85+827T>G		intron	N/A	ENSP00000435558.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	14
DANN	Benign	0.89
PhyloP100		-0.14

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: rs214070; hg19: chr11-17305317;