14-64920544-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386928.1(CHURC1):c.40-3447C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,080 control chromosomes in the GnomAD database, including 6,024 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (6024 hom., cov: 32)
• Consequence: CHURC1 NM_001386928.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237

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-FNTB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHURC1	NM_001386928.1	c.40-3447C>T		intron_variant		ENST00000549115.7
CHURC1-FNTB	NM_001202559.1	c.121-3447C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHURC1	ENST00000549115.7	c.40-3447C>T		intron_variant		1	NM_001386928.1	P1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39951 AN: 151962 Hom.: 6000 Cov.: 32

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.235

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.263 AC: 40037 AN: 152080 Hom.: 6024 Cov.: 32 AF XY: 0.265 AC XY: 19692 AN XY: 74348

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.240

Alfa AF: 0.224 Hom.: 2088

Bravo AF: 0.269

Asia WGS AF: 0.257 AC: 892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.2
Dann	Benign	0.51

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

Other links and lift over

dbSNP: rs4902336; hg19: chr14-65387262;