NM_001386928.1:c.*1121C>T

Variant names:

• chr14-64933351-C-T
• rs11158569
• NM_001386928.1:c.*1121C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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:42960): (CHURC1-FNTB readthrough) This locus represents naturally occurring read-through transcription between the neighboring CHURC1 (churchill domain containing 1) and FNTB (farnesyltransferase, CAAX box, beta) on chromosome 14. The read-through transcript produces a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386928.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHURC1	NM_001386928.1	MANE Select	c.*1121C>T		3_prime_UTR	Exon 4 of 4	NP_001373857.1	Q8WUH1-4
	CHURC1	NM_145165.4		c.*1121C>T		3_prime_UTR	Exon 4 of 4	NP_660148.4	Q8WUH1-2
	CHURC1	NM_001204064.2		c.*1152C>T		3_prime_UTR	Exon 3 of 3	NP_001190993.2	Q8WUH1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHURC1	ENST00000549115.7	TSL:1 MANE Select	c.*1121C>T		3_prime_UTR	Exon 4 of 4	ENSP00000448050.2	Q8WUH1-4
	CHURC1	ENST00000552002.7	TSL:1	c.*1121C>T		3_prime_UTR	Exon 4 of 4	ENSP00000450144.2	Q8WUH1-4
	CHURC1-FNTB	ENST00000549987.1	TSL:2	c.246+7271C>T		intron	N/A	ENSP00000447121.2	B4DL54

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

African (AFR) AF: 0.422 AC: 6638 AN: 15744

American (AMR) AF: 0.205 AC: 201 AN: 982

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1554 AN: 5140

East Asian (EAS) AF: 0.122 AC: 441 AN: 3612

South Asian (SAS) AF: 0.287 AC: 4702 AN: 16408

European-Finnish (FIN) AF: 0.237 AC: 114 AN: 482

Middle Eastern (MID) AF: 0.235 AC: 379 AN: 1616

European-Non Finnish (NFE) AF: 0.197 AC: 149598 AN: 760168

Other (OTH) AF: 0.220 AC: 5991 AN: 27252

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

African (AFR) AF: 0.405 AC: 16789 AN: 41482

American (AMR) AF: 0.205 AC: 3129 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1051 AN: 3466

East Asian (EAS) AF: 0.130 AC: 673 AN: 5180

South Asian (SAS) AF: 0.292 AC: 1411 AN: 4824

European-Finnish (FIN) AF: 0.232 AC: 2448 AN: 10564

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13825 AN: 67962

Other (OTH) AF: 0.240 AC: 507 AN: 2112

Alfa AF: 0.273 Hom.: 3175

Bravo AF: 0.270

Asia WGS AF: 0.259 AC: 900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.44
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11158569; hg19: chr14-65400069;