chr12-38903226-T-C

Variant names:

• chr12-38903226-T-C
• rs1516555
• NM_153634.3:c.98+2211A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CPNE8	NM_153634.3	c.98+2211A>G		intron_variant	Intron 1 of 19	ENST00000331366.10	NP_705898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPNE8	ENST00000331366.10	c.98+2211A>G		intron_variant	Intron 1 of 19	1	NM_153634.3	ENSP00000329748.5
CPNE8	ENST00000360449.3	c.62+4093A>G		intron_variant	Intron 1 of 19	2		ENSP00000353633.3
CPNE8	ENST00000550863.1	c.-386+2916A>G		intron_variant	Intron 1 of 7	4		ENSP00000447761.1

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

African (AFR) AF: 0.0116 AC: 481 AN: 41524

American (AMR) AF: 0.0322 AC: 492 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0464 AC: 161 AN: 3470

East Asian (EAS) AF: 0.122 AC: 631 AN: 5178

South Asian (SAS) AF: 0.0675 AC: 326 AN: 4828

European-Finnish (FIN) AF: 0.0364 AC: 386 AN: 10612

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0560 AC: 3810 AN: 68038

Other (OTH) AF: 0.0454 AC: 96 AN: 2114

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
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1516555; hg19: chr12-39297028;