dbSNP rs4073582: CNIH2:c.312-7G>A (chr11-66283241-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_182553.3(CNIH2):c.312-7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 1,613,552 control chromosomes in the GnomAD database, including 87,733 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5917 hom., cov: 32)

Exomes 𝑓: 0.33 ( 81816 hom. )

Consequence

CNIH2
NM_182553.3 splice_region, intron

Scores

Splicing: ADA: 0.0001971

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.20

Variant links:

Genes affected

CNIH2 (HGNC:28744): (cornichon family AMPA receptor auxiliary protein 2) The protein encoded by this gene is an auxiliary subunit of the ionotropic glutamate receptor of the AMPA subtype. AMPA receptors mediate fast synaptic neurotransmission in the central nervous system. This protein has been reported to interact with the Type I AMPA receptor regulatory protein isoform gamma-8 to control assembly of hippocampal AMPA receptor complexes, thereby modulating receptor gating and pharmacology. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

CNIH2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CNIH2	NM_182553.3 link	c.312-7G>A	splice_region_variant, intron_variant	Intron 4 of 5	ENST00000311445.7	NP_872359.1	Q6PI25
CNIH2	XM_047426708.1 link	c.300-7G>A	splice_region_variant, intron_variant	Intron 4 of 5		XP_047282664.1
CNIH2	NR_073078.2 link	n.620-7G>A	splice_region_variant, intron_variant	Intron 4 of 5
CNIH2	NR_073079.2 link	n.590-7G>A	splice_region_variant, intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNIH2	ENST00000311445.7 link	c.312-7G>A		splice_region_variant, intron_variant	Intron 4 of 5	1	NM_182553.3	ENSP00000310003.6		Q6PI25

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

37920

AN:

152006

Hom.:

5923

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0882

Gnomad AMI

AF:

0.483

Gnomad AMR

AF:

0.188

Gnomad ASJ

AF:

0.364

Gnomad EAS

AF:

0.0452

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.356

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.352

Gnomad OTH

AF:

0.246

GnomAD3 exomes

AF:

0.268

AC:

67292

AN:

251220

Hom.:

10541

AF XY:

0.279

AC XY:

37848

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.0846

Gnomad AMR exome

AF:

0.142

Gnomad ASJ exome

AF:

0.378

Gnomad EAS exome

AF:

0.0474

Gnomad SAS exome

AF:

0.253

Gnomad FIN exome

AF:

0.340

Gnomad NFE exome

AF:

0.346

Gnomad OTH exome

AF:

0.303

GnomAD4 exome

AF:

0.325

AC:

475460

AN:

1461428

Hom.:

81816

Cov.:

AF XY:

0.324

AC XY:

235700

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.0750

Gnomad4 AMR exome

AF:

0.147

Gnomad4 ASJ exome

AF:

0.384

Gnomad4 EAS exome

AF:

0.0624

Gnomad4 SAS exome

AF:

0.259

Gnomad4 FIN exome

AF:

0.340

Gnomad4 NFE exome

AF:

0.354

Gnomad4 OTH exome

AF:

0.302

GnomAD4 genome

AF:

0.249

AC:

37907

AN:

152124

Hom.:

5917

Cov.:

AF XY:

0.246

AC XY:

18311

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0881

Gnomad4 AMR

AF:

0.188

Gnomad4 ASJ

AF:

0.364

Gnomad4 EAS

AF:

0.0453

Gnomad4 SAS

AF:

0.239

Gnomad4 FIN

AF:

0.356

Gnomad4 NFE

AF:

0.352

Gnomad4 OTH

AF:

0.242

Alfa

AF:

0.318

Hom.:

9443

Bravo

AF:

0.228

Asia WGS

AF:

0.134

AC:

468

AN:

3478

EpiCase

AF:

0.343

EpiControl

AF:

0.357

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.6

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00020

dbscSNV1_RF

Benign

0.060

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.22

Position offset: 27

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over