dbSNP rs571596831: CPNE8:c.187-9_187-6delTTTC (chr12-38848667-GGAAA-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_153634.3(CPNE8):c.187-9_187-6delTTTC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000384 in 1,580,714 control chromosomes in the GnomAD database, including 2 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

CPNE8
NM_153634.3 splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.26

Publications

0 publications found

Variant links:

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]

CPNE8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 12-38848667-GGAAA-G is Benign according to our data. Variant chr12-38848667-GGAAA-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2642846.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153634.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPNE8	NM_153634.3	MANE Select	c.187-9_187-6delTTTC		splice_region intron	N/A	NP_705898.1	Q86YQ8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CPNE8	ENST00000331366.10	TSL:1 MANE Select	c.187-9_187-6delTTTC	splice_region intron	N/A	ENSP00000329748.5	Q86YQ8-1
CPNE8	ENST00000360449.3	TSL:2	c.151-9_151-6delTTTC	splice_region intron	N/A	ENSP00000353633.3	E7ENV7
CPNE8	ENST00000862791.1		c.187-9_187-6delTTTC	splice_region intron	N/A	ENSP00000532850.1

Frequencies

GnomAD3 genomes

AF:

0.00203

AC:

309

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00713

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.000516

AC:

113

AN:

219028

AF XY:

0.000378

show subpopulations

Gnomad AFR exome

AF:

0.00719

Gnomad AMR exome

AF:

0.000268

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000194

Gnomad OTH exome

AF:

0.000569

GnomAD4 exome

AF:

0.000207

AC:

296

AN:

1428512

Hom.:

AF XY:

0.000183

AC XY:

130

AN XY:

710018

show subpopulations

African (AFR)

AF:

0.00724

AC:

225

AN:

31080

American (AMR)

AF:

0.000302

AC:

AN:

36392

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25340

East Asian (EAS)

AF:

0.00

AC:

AN:

38450

South Asian (SAS)

AF:

0.00

AC:

AN:

79396

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52916

Middle Eastern (MID)

AF:

0.00124

AC:

AN:

4822

European-Non Finnish (NFE)

AF:

0.0000173

AC:

AN:

1101206

Other (OTH)

AF:

0.000594

AC:

AN:

58910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00204

AC:

311

AN:

152202

Hom.:

Cov.:

AF XY:

0.00202

AC XY:

150

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.00715

AC:

297

AN:

41520

American (AMR)

AF:

0.000523

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68016

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.00247

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.3

Mutation Taster

=94/6

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over