rs11158569

Positions:

• chr14-64933351-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.*1121C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 983,474 control chromosomes in the GnomAD database, including 23,993 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 (6084 hom., cov: 32)
  • Exomes 𝑓: 0.20 (17909 hom.)
• Consequence: CHURC1 NM_001386928.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.583

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 = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHURC1	NM_001386928.1	c.*1121C>T		3_prime_UTR_variant	4/4	ENST00000549115.7	NP_001373857.1
CHURC1-FNTB	NM_001202559.1	c.327+7271C>T		intron_variant			NP_001189488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHURC1	ENST00000549115.7	c.*1121C>T		3_prime_UTR_variant	4/4	1	NM_001386928.1	ENSP00000448050	P1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40151 AN: 151952 Hom.: 6059 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.204

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: 0.203

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.204 AC: 169618 AN: 831404 Hom.: 17909 Cov.: 19 AF XY: 0.205 AC XY: 78699 AN XY: 384034

Gnomad4 AFR exome AF: 0.422

Gnomad4 AMR exome AF: 0.205

Gnomad4 ASJ exome AF: 0.302

Gnomad4 EAS exome AF: 0.122

Gnomad4 SAS exome AF: 0.287

Gnomad4 FIN exome AF: 0.237

Gnomad4 NFE exome AF: 0.197

Gnomad4 OTH exome AF: 0.220

GnomAD4 genome AF: 0.265 AC: 40239 AN: 152070 Hom.: 6084 Cov.: 32 AF XY: 0.266 AC XY: 19784 AN XY: 74348

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.240

Alfa AF: 0.234 Hom.: 1135

Bravo AF: 0.270

Asia WGS AF: 0.259 AC: 900 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	1.6
DANN	Benign	0.44

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: rs11158569; hg19: chr14-65400069;