1-224728890-C-T

Variant names:

• chr1-224728890-C-T
• rs6660579
• NM_152495.2:c.199-1572C>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.199-1572C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,214 control chromosomes in the GnomAD database, including 1,209 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 0.12 (1209 hom., cov: 32)
• Consequence: CNIH3 NM_152495.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.432
• Publications: 4 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]

CNIH3-AS1 (HGNC:41163): (CNIH3 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.191 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNIH3	NM_152495.2	MANE Select	c.199-1572C>T		intron	N/A	NP_689708.1
	CNIH3	NM_001322302.2		c.283-1572C>T		intron	N/A	NP_001309231.1
	CNIH3	NM_001322303.2		c.217-1572C>T		intron	N/A	NP_001309232.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNIH3	ENST00000272133.4	TSL:1 MANE Select	c.199-1572C>T		intron	N/A	ENSP00000272133.3
	CNIH3-AS1	ENST00000431691.1	TSL:3	n.365+1408G>A		intron	N/A
	CNIH3	ENST00000478120.5	TSL:5	n.520-1572C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18911 AN: 152096 Hom.: 1209 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.0885

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.124 AC: 18922 AN: 152214 Hom.: 1209 Cov.: 32 AF XY: 0.124 AC XY: 9248 AN XY: 74420

African (AFR) AF: 0.109 AC: 4507 AN: 41530

American (AMR) AF: 0.147 AC: 2254 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 471 AN: 3468

East Asian (EAS) AF: 0.160 AC: 830 AN: 5186

South Asian (SAS) AF: 0.201 AC: 970 AN: 4816

European-Finnish (FIN) AF: 0.0885 AC: 937 AN: 10590

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8504 AN: 68004

Other (OTH) AF: 0.139 AC: 294 AN: 2110

Alfa AF: 0.128 Hom.: 3813

Bravo AF: 0.127

Asia WGS AF: 0.167 AC: 578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.74
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs6660579; hg19: chr1-224916592;