ENST00000549987.1:c.246+19110C>A

Variant names:

• chr14-64945190-C-A
• rs3742599
• ENST00000549987.1:c.246+19110C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000549987.1(CHURC1-FNTB):​c.246+19110C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,214 control chromosomes in the GnomAD database, including 1,775 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 0.15 (1775 hom., cov: 33)
• Consequence: CHURC1-FNTB ENST00000549987.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 13 publications found

Genes affected

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHURC1-FNTB	NM_001202559.1	c.327+19110C>A		intron_variant	Intron 3 of 13		NP_001189488.1
CHURC1-FNTB	NM_001202558.2	c.6+21064C>A		intron_variant	Intron 2 of 12		NP_001189487.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHURC1-FNTB	ENST00000549987.1	c.246+19110C>A		intron_variant	Intron 3 of 13	2		ENSP00000447121.2
CHURC1-FNTB	ENST00000553743.5	c.91+21064C>A		intron_variant	Intron 1 of 2	2		ENSP00000450692.1
CHURC1-FNTB	ENST00000551823.1	n.*62+12898C>A		intron_variant	Intron 3 of 5	2		ENSP00000449709.1
CHURC1-FNTB	ENST00000552941.6	n.175+21064C>A		intron_variant	Intron 2 of 12	2		ENSP00000449668.2

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22106 AN: 152096 Hom.: 1773 Cov.: 33

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0725

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.145 AC: 22131 AN: 152214 Hom.: 1775 Cov.: 33 AF XY: 0.148 AC XY: 11007 AN XY: 74406

African (AFR) AF: 0.101 AC: 4183 AN: 41542

American (AMR) AF: 0.119 AC: 1826 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 592 AN: 3472

East Asian (EAS) AF: 0.0727 AC: 377 AN: 5186

South Asian (SAS) AF: 0.118 AC: 571 AN: 4828

European-Finnish (FIN) AF: 0.213 AC: 2250 AN: 10584

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11676 AN: 67998

Other (OTH) AF: 0.131 AC: 277 AN: 2114

Alfa AF: 0.164 Hom.: 2280

Bravo AF: 0.138

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.037
DANN	Benign	0.78
PhyloP100		-1.8
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: rs3742599; hg19: chr14-65411908;