rs4073582

Variant names:

• chr11-66283241-G-A
• rs4073582
• NM_182553.3:c.312-7G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-66283241-G-A
• chr11-66283241-G-C

Variant summary

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

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
• Publications: 32 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNIH2	NM_182553.3	c.312-7G>A		splice_region_variant, intron_variant	Intron 4 of 5	ENST00000311445.7	NP_872359.1
CNIH2	NR_073078.2	n.620-7G>A		splice_region_variant, intron_variant	Intron 4 of 5
CNIH2	NR_073079.2	n.590-7G>A		splice_region_variant, intron_variant	Intron 4 of 5
CNIH2	XM_047426708.1	c.300-7G>A		splice_region_variant, intron_variant	Intron 4 of 5		XP_047282664.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37920 AN: 152006 Hom.: 5923 Cov.: 32

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

GnomAD2 exomes AF: 0.268 AC: 67292 AN: 251220 AF XY: 0.279

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 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.: 48 AF XY: 0.324 AC XY: 235700 AN XY: 727028

African (AFR) AF: 0.0750 AC: 2510 AN: 33478

American (AMR) AF: 0.147 AC: 6572 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 10036 AN: 26136

East Asian (EAS) AF: 0.0624 AC: 2478 AN: 39700

South Asian (SAS) AF: 0.259 AC: 22336 AN: 86256

European-Finnish (FIN) AF: 0.340 AC: 18100 AN: 53228

Middle Eastern (MID) AF: 0.295 AC: 1703 AN: 5766

European-Non Finnish (NFE) AF: 0.354 AC: 393497 AN: 1111768

Other (OTH) AF: 0.302 AC: 18228 AN: 60376

GnomAD4 genome AF: 0.249 AC: 37907 AN: 152124 Hom.: 5917 Cov.: 32 AF XY: 0.246 AC XY: 18311 AN XY: 74362

African (AFR) AF: 0.0881 AC: 3660 AN: 41532

American (AMR) AF: 0.188 AC: 2868 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1261 AN: 3468

East Asian (EAS) AF: 0.0453 AC: 234 AN: 5168

South Asian (SAS) AF: 0.239 AC: 1152 AN: 4822

European-Finnish (FIN) AF: 0.356 AC: 3773 AN: 10592

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23940 AN: 67946

Other (OTH) AF: 0.242 AC: 512 AN: 2112

Alfa AF: 0.311 Hom.: 22001

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
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4073582; hg19: chr11-66050712; COSMIC: COSV61012494; COSMIC: COSV61012494;