Variant 14-64924121-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001386928.1(CHURC1):c.170A>G(p.Tyr57Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00385 in 1,607,926 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0039 ( 21 hom. )

Consequence

CHURC1
NM_001386928.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 8.05

Variant links:

Genes affected

CHURC1 (HGNC:20099): (churchill domain containing 1) Predicted to enable zinc ion binding activity. Predicted to be involved in positive regulation of transcription, DNA-templated. [provided by Alliance of Genome Resources, Apr 2022]

CHURC1 links:

CHURC1-FNTB (HGNC:):

CHURC1-FNTB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012085617).

BP6

Variant 14-64924121-A-G is Benign according to our data. Variant chr14-64924121-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 782958.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHURC1	NM_001386928.1 linkuse as main transcript	c.170A>G	p.Tyr57Cys	missense_variant	2/4	ENST00000549115.7	NP_001373857.1
CHURC1-FNTB	NM_001202559.1 linkuse as main transcript	c.251A>G	p.Tyr84Cys	missense_variant	2/14		NP_001189488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHURC1	ENST00000549115.7 linkuse as main transcript	c.170A>G	p.Tyr57Cys	missense_variant	2/4	1	NM_001386928.1	ENSP00000448050	P1	Q8WUH1-4

Frequencies

GnomAD3 genomes

AF:

0.00302

AC:

460

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00905

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00484

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00352

AC:

870

AN:

247434

Hom.:

AF XY:

0.00341

AC XY:

457

AN XY:

133848

show subpopulations

Gnomad AFR exome

AF:

0.000992

Gnomad AMR exome

AF:

0.000303

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000336

Gnomad FIN exome

AF:

0.00836

Gnomad NFE exome

AF:

0.00573

Gnomad OTH exome

AF:

0.00284

GnomAD4 exome

AF:

0.00394

AC:

5729

AN:

1455594

Hom.:

Cov.:

AF XY:

0.00376

AC XY:

2722

AN XY:

723988

show subpopulations

Gnomad4 AFR exome

AF:

0.000540

Gnomad4 AMR exome

AF:

0.000365

Gnomad4 ASJ exome

AF:

0.000154

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000471

Gnomad4 FIN exome

AF:

0.00946

Gnomad4 NFE exome

AF:

0.00452

Gnomad4 OTH exome

AF:

0.00293

GnomAD4 genome

AF:

0.00302

AC:

460

AN:

152332

Hom.:

Cov.:

AF XY:

0.00285

AC XY:

212

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00905

Gnomad4 NFE

AF:

0.00484

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00372

Hom.:

Bravo

AF:

0.00238

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00547

AC:

ExAC

AF:

0.00400

AC:

486

Asia WGS

AF:

0.000867

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 19, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	CHURC1: BS2; CHURC1-FNTB: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

T;.;.;.;.;.

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;T;D;D;D;D

M_CAP

Benign

0.077

MetaRNN

Benign

0.012

T;T;T;T;T;T

MetaSVM

Uncertain

-0.27

MutationTaster

Benign

1.0

D;D;D;D;D;N

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-7.4

D;.;D;.;.;D

REVEL

Uncertain

0.38

Sift

Uncertain

0.0010

D;.;D;.;.;D

Sift4G

Pathogenic

0.0010

D;D;D;D;D;D

Polyphen

0.12

.;.;.;.;B;.

Vest4

0.97

MVP

0.56

MPC

0.81

ClinPred

0.10

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.80

gMVP

0.77

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

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