12-38903226-T-C

Position:

• chr12-38903226-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_153634.3(CPNE8):​c.98+2211A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 152,270 control chromosomes in the GnomAD database, including 168 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 0.042 (168 hom., cov: 33)
• Consequence: CPNE8 NM_153634.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

Genes affected

CPNE8 (HGNC:23498): (copine 8) Calcium-dependent membrane-binding proteins may regulate molecular events at the interface of the cell membrane and cytoplasm. This gene is one of several genes that encode a calcium-dependent protein containing two N-terminal type II C2 domains and an integrin A domain-like sequence in the C-terminus. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPNE8	NM_153634.3	c.98+2211A>G		intron_variant		ENST00000331366.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPNE8	ENST00000331366.10	c.98+2211A>G		intron_variant		1	NM_153634.3	P1
CPNE8	ENST00000360449.3	c.62+4093A>G		intron_variant		2
CPNE8	ENST00000550863.1	c.-386+2916A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0422 AC: 6419 AN: 152152 Hom.: 168 Cov.: 33

Gnomad AFR AF: 0.0116

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0322

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.0671

Gnomad FIN AF: 0.0364

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0560

Gnomad OTH AF: 0.0464

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

GnomAD4 genome AF: 0.0421 AC: 6416 AN: 152270 Hom.: 168 Cov.: 33 AF XY: 0.0419 AC XY: 3121 AN XY: 74442

Gnomad4 AFR AF: 0.0116

Gnomad4 AMR AF: 0.0322

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.0675

Gnomad4 FIN AF: 0.0364

Gnomad4 NFE AF: 0.0560

Gnomad4 OTH AF: 0.0454

Alfa AF: 0.0238 Hom.: 19

Bravo AF: 0.0403

Asia WGS AF: 0.0920 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.0
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: 1

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

Publications

LitVar

Other links and lift over

dbSNP: rs1516555; hg19: chr12-39297028;