17-66980458-G-A

Position:

• chr17-66980458-G-A

Variant summary

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

The NM_014405.4(CACNG4):​c.220+15327G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 151,916 control chromosomes in the GnomAD database, including 33,895 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 0.66 (33895 hom., cov: 31)
• Consequence: CACNG4 NM_014405.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.683

Genes affected

CACNG4 (HGNC:1408): (calcium voltage-gated channel auxiliary subunit gamma 4) The protein encoded by this gene is a type I transmembrane AMPA receptor regulatory protein (TARP). TARPs regulate both trafficking and channel gating of the AMPA receptors. This gene is part of a functionally diverse eight-member protein subfamily of the PMP-22/EMP/MP20 family and is located in a cluster with two family members, a type II TARP and a calcium channel gamma subunit. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNG4	NM_014405.4	c.220+15327G>A		intron_variant		ENST00000262138.4	NP_055220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNG4	ENST00000262138.4	c.220+15327G>A		intron_variant		1	NM_014405.4	ENSP00000262138	P1

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99527 AN: 151798 Hom.: 33859 Cov.: 31

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.656 AC: 99608 AN: 151916 Hom.: 33895 Cov.: 31 AF XY: 0.647 AC XY: 48070 AN XY: 74240

Gnomad4 AFR AF: 0.852

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.618

Alfa AF: 0.634 Hom.: 6934

Bravo AF: 0.671

Asia WGS AF: 0.587 AC: 2044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.26
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs4790896; hg19: chr17-64976574;