rs12979328

Variant names:

• chr19-48921124-C-A
• rs12979328
• NM_006184.6:c.1003-30C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-48921124-C-A
• chr19-48921124-C-T

Variant summary

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

The NM_006184.6(NUCB1):​c.1003-30C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 1,575,636 control chromosomes in the GnomAD database, including 377,775 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 0.53 (26501 hom., cov: 33)
  • Exomes 𝑓: 0.69 (351274 hom.)
• Consequence: NUCB1 NM_006184.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.924
• Publications: 13 publications found

Genes affected

NUCB1 (HGNC:8043): (nucleobindin 1) This gene encodes a member of a small calcium-binding EF-hand protein family. The encoded protein is thought to have a key role in Golgi calcium homeostasis and Ca(2+)-regulated signal transduction events. [provided by RefSeq, Jun 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006184.6. 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
	NUCB1	NM_006184.6	MANE Select	c.1003-30C>A		intron	N/A	NP_006175.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUCB1	ENST00000405315.9	TSL:1 MANE Select	c.1003-30C>A		intron	N/A	ENSP00000385923.3
	NUCB1	ENST00000706750.1		n.*1229C>A		non_coding_transcript_exon	Exon 11 of 13	ENSP00000516528.1
	NUCB1	ENST00000706752.1		n.*1674C>A		non_coding_transcript_exon	Exon 10 of 12	ENSP00000516530.1

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80879 AN: 151966 Hom.: 26510 Cov.: 33

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.551

GnomAD2 exomes AF: 0.629 AC: 142795 AN: 227122 AF XY: 0.648

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.543

Gnomad ASJ exome AF: 0.648

Gnomad EAS exome AF: 0.396

Gnomad FIN exome AF: 0.760

Gnomad NFE exome AF: 0.721

Gnomad OTH exome AF: 0.653

GnomAD4 exome AF: 0.693 AC: 986689 AN: 1423550 Hom.: 351274 Cov.: 36 AF XY: 0.696 AC XY: 489800 AN XY: 703542

African (AFR) AF: 0.118 AC: 3814 AN: 32318

American (AMR) AF: 0.551 AC: 22041 AN: 40026

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 15703 AN: 24172

East Asian (EAS) AF: 0.369 AC: 14430 AN: 39082

South Asian (SAS) AF: 0.707 AC: 58261 AN: 82352

European-Finnish (FIN) AF: 0.758 AC: 39025 AN: 51514

Middle Eastern (MID) AF: 0.620 AC: 3424 AN: 5520

European-Non Finnish (NFE) AF: 0.727 AC: 792300 AN: 1090068

Other (OTH) AF: 0.644 AC: 37691 AN: 58498

GnomAD4 genome AF: 0.532 AC: 80876 AN: 152086 Hom.: 26501 Cov.: 33 AF XY: 0.537 AC XY: 39892 AN XY: 74328

African (AFR) AF: 0.139 AC: 5751 AN: 41508

American (AMR) AF: 0.553 AC: 8431 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2193 AN: 3470

East Asian (EAS) AF: 0.388 AC: 2001 AN: 5154

South Asian (SAS) AF: 0.711 AC: 3430 AN: 4826

European-Finnish (FIN) AF: 0.770 AC: 8139 AN: 10574

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.720 AC: 48976 AN: 67996

Other (OTH) AF: 0.549 AC: 1155 AN: 2104

Alfa AF: 0.685 Hom.: 47046

Bravo AF: 0.496

Asia WGS AF: 0.562 AC: 1953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.7
DANN	Benign	0.84
PhyloP100		0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12979328; hg19: chr19-49424381; COSMIC: COSV107207108; COSMIC: COSV107207108;