14-64920544-C-T

Variant names:

• chr14-64920544-C-T
• rs4902336
• NM_001386928.1:c.40-3447C>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.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
• Publications: 20 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 = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHURC1	NM_001386928.1	c.40-3447C>T		intron_variant	Intron 1 of 3	ENST00000549115.7	NP_001373857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHURC1	ENST00000549115.7	c.40-3447C>T		intron_variant	Intron 1 of 3	1	NM_001386928.1	ENSP00000448050.2
CHURC1-FNTB	ENST00000549987.1	c.40-3447C>T		intron_variant	Intron 1 of 13	2		ENSP00000447121.2

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

African (AFR) AF: 0.400 AC: 16592 AN: 41464

American (AMR) AF: 0.204 AC: 3112 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1052 AN: 3472

East Asian (EAS) AF: 0.130 AC: 674 AN: 5180

South Asian (SAS) AF: 0.292 AC: 1412 AN: 4828

European-Finnish (FIN) AF: 0.232 AC: 2446 AN: 10562

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

European-Non Finnish (NFE) AF: 0.204 AC: 13836 AN: 67980

Other (OTH) AF: 0.240 AC: 505 AN: 2108

Alfa AF: 0.225 Hom.: 3055

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
PhyloP100		-0.24
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: rs4902336; hg19: chr14-65387262;