rs1064108

Variant names:

• chr14-64933547-C-T
• rs1064108
• NM_001386928.1:c.*1317C>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.*1317C>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 0.326 in 976,432 control chromosomes in the GnomAD database, including 60,765 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 0.47 (20400 hom., cov: 32)
  • Exomes 𝑓: 0.30 (40365 hom.)
• Consequence: CHURC1 NM_001386928.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320
• Publications: 18 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.798 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.*1317C>T		3_prime_UTR	Exon 4 of 4	NP_001373857.1
	CHURC1	NM_145165.4		c.*1317C>T		3_prime_UTR	Exon 4 of 4	NP_660148.4
	CHURC1	NM_001204064.2		c.*1348C>T		3_prime_UTR	Exon 3 of 3	NP_001190993.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHURC1	ENST00000549115.7	TSL:1 MANE Select	c.*1317C>T		3_prime_UTR	Exon 4 of 4	ENSP00000448050.2
	CHURC1	ENST00000552002.7	TSL:1	c.*1317C>T		3_prime_UTR	Exon 4 of 4	ENSP00000450144.2
	CHURC1-FNTB	ENST00000549987.1	TSL:2	c.246+7467C>T		intron	N/A	ENSP00000447121.2

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70569 AN: 151866 Hom.: 20346 Cov.: 32

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.433

GnomAD4 exome AF: 0.300 AC: 247323 AN: 824448 Hom.: 40365 Cov.: 17 AF XY: 0.300 AC XY: 114139 AN XY: 381068

African (AFR) AF: 0.853 AC: 13269 AN: 15564

American (AMR) AF: 0.369 AC: 362 AN: 980

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1982 AN: 5086

East Asian (EAS) AF: 0.704 AC: 2519 AN: 3578

South Asian (SAS) AF: 0.367 AC: 5981 AN: 16276

European-Finnish (FIN) AF: 0.351 AC: 97 AN: 276

Middle Eastern (MID) AF: 0.364 AC: 584 AN: 1604

European-Non Finnish (NFE) AF: 0.283 AC: 213078 AN: 754118

Other (OTH) AF: 0.350 AC: 9451 AN: 26966

GnomAD4 genome AF: 0.465 AC: 70685 AN: 151984 Hom.: 20400 Cov.: 32 AF XY: 0.467 AC XY: 34662 AN XY: 74268

African (AFR) AF: 0.805 AC: 33418 AN: 41492

American (AMR) AF: 0.365 AC: 5574 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1332 AN: 3466

East Asian (EAS) AF: 0.714 AC: 3687 AN: 5166

South Asian (SAS) AF: 0.393 AC: 1893 AN: 4822

European-Finnish (FIN) AF: 0.355 AC: 3727 AN: 10500

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19637 AN: 67938

Other (OTH) AF: 0.438 AC: 924 AN: 2112

Alfa AF: 0.371 Hom.: 24281

Bravo AF: 0.488

Asia WGS AF: 0.560 AC: 1946 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.53
PhyloP100		0.032
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: rs1064108; hg19: chr14-65400265;