6-36745524-C-T

Variant names:

• chr6-36745524-C-T
• rs146907172
• NM_020939.2:c.1201-9G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_020939.2(CPNE5):​c.1201-9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000399 in 1,597,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: CPNE5 NM_020939.2 intron
• Scores: Splicing: ADA: 0.0001600
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.650
• Publications: 0 publications found

Genes affected

CPNE5 (HGNC:2318): (copine 5) 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. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. More variants may exist, but their full-length natures could not be determined. [provided by RefSeq, Sep 2015]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 6-36745524-C-T is Benign according to our data. Variant chr6-36745524-C-T is described in ClinVar as Benign. ClinVar VariationId is 773196.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020939.2. 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
	CPNE5	NM_020939.2	MANE Select	c.1201-9G>A		intron	N/A	NP_065990.1	Q9HCH3-1
	CPNE5	NM_001410887.1		c.1252-9G>A		intron	N/A	NP_001397816.1	A0A0J9YWA1
	CPNE5	NM_001376889.1		c.1252-9G>A		intron	N/A	NP_001363818.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPNE5	ENST00000244751.7	TSL:1 MANE Select	c.1201-9G>A		intron	N/A	ENSP00000244751.2	Q9HCH3-1
	CPNE5	ENST00000393189.2	TSL:1	c.325-9G>A		intron	N/A	ENSP00000376885.2	Q9HCH3-2
	CPNE5	ENST00000493411.2	TSL:1	n.381-9G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00233 AC: 354 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00806

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000513 AC: 113 AN: 220376 AF XY: 0.000438

Gnomad AFR exome AF: 0.00726

Gnomad AMR exome AF: 0.000478

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000196 AC: 283 AN: 1445290 Hom.: 0 Cov.: 33 AF XY: 0.000178 AC XY: 128 AN XY: 717112

African (AFR) AF: 0.00698 AC: 232 AN: 33250

American (AMR) AF: 0.000546 AC: 23 AN: 42140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25658

East Asian (EAS) AF: 0.00 AC: 0 AN: 39040

South Asian (SAS) AF: 0.0000360 AC: 3 AN: 83238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.00000362 AC: 4 AN: 1104222

Other (OTH) AF: 0.000351 AC: 21 AN: 59816

GnomAD4 genome AF: 0.00232 AC: 354 AN: 152264 Hom.: 0 Cov.: 32 AF XY: 0.00235 AC XY: 175 AN XY: 74436

African (AFR) AF: 0.00804 AC: 334 AN: 41554

American (AMR) AF: 0.000915 AC: 14 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00116 Hom.: 1

Bravo AF: 0.00270

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.9
DANN	Benign	0.94
PhyloP100		0.65
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00016
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs146907172; hg19: chr6-36713301;