Variant 17-63752432-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020198.3(CCDC47):c.1094-3C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00315 in 1,589,742 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 72 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 63 hom. )

Consequence

CCDC47
NM_020198.3 splice_region, intron

Scores

Splicing: ADA: 0.004312

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.859

Variant links:

Genes affected

CCDC47 (HGNC:24856): (coiled-coil domain containing 47) Enables protein folding chaperone and ribosome binding activity. Involved in ERAD pathway; endoplasmic reticulum calcium ion homeostasis; and protein insertion into ER membrane. Located in endoplasmic reticulum. Is integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

CCDC47 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 17-63752432-G-A is Benign according to our data. Variant chr17-63752432-G-A is described in ClinVar as [Benign]. Clinvar id is 768908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC47	NM_020198.3 linkuse as main transcript	c.1094-3C>T		splice_region_variant, intron_variant		ENST00000225726.10	NP_064583.2	Q96A33-1
CCDC47	XM_005257527.3 linkuse as main transcript	c.1094-3C>T		splice_region_variant, intron_variant			XP_005257584.1	Q96A33-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CCDC47	ENST00000225726.10 linkuse as main transcript	c.1094-3C>T	splice_region_variant, intron_variant	1	NM_020198.3	ENSP00000225726.5	Q96A33-1
CCDC47	ENST00000403162.7 linkuse as main transcript	c.1094-3C>T	splice_region_variant, intron_variant	2		ENSP00000384888.3	Q96A33-1
CCDC47	ENST00000582252.1 linkuse as main transcript	c.1094-3C>T	splice_region_variant, intron_variant	2		ENSP00000463577.1	Q96A33-2

Frequencies

GnomAD3 genomes

AF:

0.0170

AC:

2579

AN:

151586

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0588

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00710

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.00433

AC:

1053

AN:

243442

Hom.:

AF XY:

0.00318

AC XY:

418

AN XY:

131612

show subpopulations

Gnomad AFR exome

AF:

0.0596

Gnomad AMR exome

AF:

0.00216

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000175

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000807

Gnomad OTH exome

AF:

0.00168

GnomAD4 exome

AF:

0.00169

AC:

2428

AN:

1438058

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

1042

AN XY:

716212

show subpopulations

Gnomad4 AFR exome

AF:

0.0621

Gnomad4 AMR exome

AF:

0.00254

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000143

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000530

Gnomad4 OTH exome

AF:

0.00335

GnomAD4 genome

AF:

0.0170

AC:

2583

AN:

151684

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

1192

AN XY:

74056

show subpopulations

Gnomad4 AFR

AF:

0.0588

Gnomad4 AMR

AF:

0.00709

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.0162

Alfa

AF:

0.00771

Hom.:

Bravo

AF:

0.0197

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 11, 2018	- -

CCDC47-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 04, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

8.1

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0043

dbscSNV1_RF

Benign

0.088

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

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