rs7113041

Variant names:

• chr11-124742695-C-G
• rs7113041
• NM_006176.3:c.15+2596C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006176.3. 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
	NRGN	NM_006176.3	MANE Select	c.15+2596C>G		intron	N/A	NP_006167.1
	NRGN	NM_001126181.2		c.15+2596C>G		intron	N/A	NP_001119653.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRGN	ENST00000284292.11	TSL:1 MANE Select	c.15+2596C>G		intron	N/A	ENSP00000284292.5
	NRGN	ENST00000412681.2	TSL:1	c.15+2596C>G		intron	N/A	ENSP00000399591.1
	NRGN	ENST00000893844.1		c.15+2596C>G		intron	N/A	ENSP00000563903.1

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

African (AFR) AF: 0.604 AC: 25005 AN: 41400

American (AMR) AF: 0.203 AC: 3109 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1039 AN: 3468

East Asian (EAS) AF: 0.227 AC: 1170 AN: 5164

South Asian (SAS) AF: 0.205 AC: 987 AN: 4824

European-Finnish (FIN) AF: 0.210 AC: 2222 AN: 10566

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17664 AN: 67972

Other (OTH) AF: 0.309 AC: 654 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	14
DANN	Benign	0.63
PhyloP100		0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7113041; hg19: chr11-124612591;