chr11-124742695-C-G

Position:

• chr11-124742695-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_006176.3(NRGN):​c.15+2596C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 151,990 control chromosomes in the GnomAD database, including 10,965 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 0.34 (10965 hom., cov: 32)
• Consequence: NRGN NM_006176.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.616

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRGN	NM_006176.3	c.15+2596C>G		intron_variant		ENST00000284292.11	NP_006167.1
NRGN	NM_001126181.2	c.15+2596C>G		intron_variant			NP_001119653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRGN	ENST00000284292.11	c.15+2596C>G		intron_variant		1	NM_006176.3	ENSP00000284292	P1
NRGN	ENST00000412681.2	c.15+2596C>G		intron_variant		1		ENSP00000399591	P1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52032 AN: 151870 Hom.: 10935 Cov.: 32

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.343 AC: 52108 AN: 151990 Hom.: 10965 Cov.: 32 AF XY: 0.332 AC XY: 24639 AN XY: 74302

Gnomad4 AFR AF: 0.604

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.309

Alfa AF: 0.320 Hom.: 1125

Bravo AF: 0.354

Asia WGS AF: 0.258 AC: 895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	14
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.22		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7113041; hg19: chr11-124612591;