rs12278912

Positions:

• chr11-124742263-G-A
• chr11-124742263-G-T

Variant summary

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

The NM_006176.3(NRGN):​c.15+2164G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 151,898 control chromosomes in the GnomAD database, including 9,092 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 0.32 (9092 hom., cov: 31)
• Consequence: NRGN NM_006176.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449

Genes affected

NRGN (HGNC:8000): (neurogranin) Neurogranin (NRGN) is the human homolog of the neuron-specific rat RC3/neurogranin gene. This gene encodes a postsynaptic protein kinase substrate that binds calmodulin in the absence of calcium. The NRGN gene contains four exons and three introns. The exons 1 and 2 encode the protein and exons 3 and 4 contain untranslated sequences. It is suggested that the NRGN is a direct target for thyroid hormone in human brain, and that control of expression of this gene could underlay many of the consequences of hypothyroidism on mental states during development as well as in adult subjects. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRGN	NM_006176.3	c.15+2164G>A		intron_variant		ENST00000284292.11
NRGN	NM_001126181.2	c.15+2164G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRGN	ENST00000284292.11	c.15+2164G>A		intron_variant		1	NM_006176.3	P1
NRGN	ENST00000412681.2	c.15+2164G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48591 AN: 151780 Hom.: 9062 Cov.: 31

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.320 AC: 48662 AN: 151898 Hom.: 9092 Cov.: 31 AF XY: 0.310 AC XY: 22994 AN XY: 74224

Gnomad4 AFR AF: 0.531

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.289

Alfa AF: 0.260 Hom.: 10811

Bravo AF: 0.328

Asia WGS AF: 0.252 AC: 874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.9
DANN	Benign	0.80

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: rs12278912; hg19: chr11-124612159;