1-224437373-T-C

Position:

• chr1-224437373-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001322302.2(CNIH3):​c.99+2186T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 152,162 control chromosomes in the GnomAD database, including 28,550 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 0.57 (28550 hom., cov: 32)
• Consequence: CNIH3 NM_001322302.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNIH3	NM_001322302.2	c.99+2186T>C		intron_variant			NP_001309231.1
CNIH3	NM_001322303.2	c.99+2186T>C		intron_variant			NP_001309232.1
CNIH3	NM_001322304.2	c.-118+2186T>C		intron_variant			NP_001309233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNIH3	ENST00000471578.5	n.203+2511T>C		intron_variant		5
CNIH3	ENST00000483512.5	n.276+2186T>C		intron_variant		2
CNIH3	ENST00000498126.5	n.263+2186T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86645 AN: 152044 Hom.: 28535 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.960

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.570 AC: 86673 AN: 152162 Hom.: 28550 Cov.: 32 AF XY: 0.575 AC XY: 42805 AN XY: 74380

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.722

Gnomad4 ASJ AF: 0.657

Gnomad4 EAS AF: 0.960

Gnomad4 SAS AF: 0.636

Gnomad4 FIN AF: 0.692

Gnomad4 NFE AF: 0.688

Gnomad4 OTH AF: 0.598

Alfa AF: 0.665 Hom.: 54115

Bravo AF: 0.562

Asia WGS AF: 0.721 AC: 2509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10799573; hg19: chr1-224625075;