1-224677050-A-T

Variant names:

• chr1-224677050-A-T
• rs1369847
• NM_152495.2:c.82-3908A>T

Variant summary

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

The NM_152495.2(CNIH3):​c.82-3908A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 152,088 control chromosomes in the GnomAD database, including 15,116 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 0.41 (15116 hom., cov: 32)
• Consequence: CNIH3 NM_152495.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.538
• Publications: 2 publications found

Genes affected

CNIH3 (HGNC:26802): (cornichon family AMPA receptor auxiliary protein 3) Predicted to enable channel regulator activity. Involved in regulation of AMPA receptor activity. Predicted to be located in dendritic shaft and postsynaptic membrane. Predicted to be part of AMPA glutamate receptor complex. Predicted to be active in dendrite and glutamatergic synapse. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152495.2. 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
	CNIH3	NM_152495.2	MANE Select	c.82-3908A>T		intron	N/A	NP_689708.1	Q8TBE1
	CNIH3	NM_001322302.2		c.166-3908A>T		intron	N/A	NP_001309231.1
	CNIH3	NM_001322303.2		c.100-3908A>T		intron	N/A	NP_001309232.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNIH3	ENST00000272133.4	TSL:1 MANE Select	c.82-3908A>T		intron	N/A	ENSP00000272133.3	Q8TBE1
	CNIH3	ENST00000860910.1		c.82-3908A>T		intron	N/A	ENSP00000530969.1
	CNIH3	ENST00000933029.1		c.82-53412A>T		intron	N/A	ENSP00000603088.1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62555 AN: 151970 Hom.: 15117 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.411 AC: 62556 AN: 152088 Hom.: 15116 Cov.: 32 AF XY: 0.405 AC XY: 30095 AN XY: 74350

African (AFR) AF: 0.165 AC: 6841 AN: 41506

American (AMR) AF: 0.404 AC: 6168 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2218 AN: 3468

East Asian (EAS) AF: 0.227 AC: 1177 AN: 5186

South Asian (SAS) AF: 0.487 AC: 2342 AN: 4808

European-Finnish (FIN) AF: 0.429 AC: 4531 AN: 10568

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.554 AC: 37664 AN: 67956

Other (OTH) AF: 0.459 AC: 972 AN: 2116

Alfa AF: 0.478 Hom.: 2345

Bravo AF: 0.393

Asia WGS AF: 0.381 AC: 1325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.1
DANN	Benign	0.92
PhyloP100		0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1369847; hg19: chr1-224864752; COSMIC: COSV107236818;