Variant 1-3754148-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_152492.3(CCDC27):c.349G>A(p.Gly117Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,613,608 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 1 hom. )

Consequence

CCDC27
NM_152492.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.289

Variant links:

Genes affected

CCDC27 (HGNC:26546): (coiled-coil domain containing 27)

CCDC27 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020818383).

BP6

Variant 1-3754148-G-A is Benign according to our data. Variant chr1-3754148-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3139078.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC27	NM_152492.3 linkuse as main transcript	c.349G>A	p.Gly117Ser	missense_variant	2/12	ENST00000294600.7	NP_689705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CCDC27	ENST00000294600.7 linkuse as main transcript	c.349G>A	p.Gly117Ser	missense_variant	2/12	1	NM_152492.3	ENSP00000294600	P1
CCDC27	ENST00000636250.1 linkuse as main transcript	n.859G>A		non_coding_transcript_exon_variant	5/6	5
CCDC27	ENST00000462521.2 linkuse as main transcript	c.349G>A	p.Gly117Ser	missense_variant, NMD_transcript_variant	2/12	5		ENSP00000463275

Frequencies

GnomAD3 genomes

AF:

0.000736

AC:

112

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000526

AC:

132

AN:

250904

Hom.:

AF XY:

0.000553

AC XY:

AN XY:

135636

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00102

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00116

AC:

1689

AN:

1461374

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

815

AN XY:

727014

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.00138

Gnomad4 OTH exome

AF:

0.00209

GnomAD4 genome

AF:

0.000736

AC:

112

AN:

152234

Hom.:

Cov.:

AF XY:

0.000699

AC XY:

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00105

Hom.:

Bravo

AF:

0.000669

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.000469

AC:

EpiCase

AF:

0.00109

EpiControl

AF:

0.00119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 09, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.85

DANN

Benign

0.40

DEOGEN2

Benign

0.0050

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00096

LIST_S2

Benign

0.40

M_CAP

Benign

0.0029

MetaRNN

Benign

0.021

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.99

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.1

REVEL

Benign

0.0070

Sift

Benign

0.21

Sift4G

Benign

0.45

Polyphen

0.027

Vest4

0.21

MVP

0.014

MPC

0.13

ClinPred

0.016

GERP RS

-3.9

Varity_R

0.031

gMVP

0.064

Splicing

Name

Calibrated prediction

Score

Prediction

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over