chr4-64404404-A-G

Variant names:

• chr4-64404404-A-G
• rs10517893
• NM_001010874.5:c.234+4714T>C

Variant summary

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

The NM_001010874.5(TECRL):​c.234+4714T>C 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 151,872 control chromosomes in the GnomAD database, including 5,495 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 (5495 hom., cov: 32)
• Consequence: TECRL NM_001010874.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.571
• Publications: 8 publications found

Genes affected

TECRL (HGNC:27365): (trans-2,3-enoyl-CoA reductase like) The protein encoded by this gene contains a ubiquitin-like domain in the N-terminal region, three transmembrane segments and a C-terminal 3-oxo-5-alpha steroid 4-dehydrogenase domain. The protein belongs to the steroid 5-alpha reductase family. Mutations in this gene result in ventricular tachycardia, catecholaminergic polymorphic, 3. [provided by RefSeq, Apr 2017]

TECRL Gene-Disease associations (from GenCC):

• catecholaminergic polymorphic ventricular tachycardia

  Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• catecholaminergic polymorphic ventricular tachycardia 3

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECRL	NM_001010874.5	c.234+4714T>C		intron_variant	Intron 1 of 11	ENST00000381210.8	NP_001010874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TECRL	ENST00000381210.8	c.234+4714T>C		intron_variant	Intron 1 of 11	1	NM_001010874.5	ENSP00000370607.3
TECRL	ENST00000511356.1	n.339+4714T>C		intron_variant	Intron 1 of 6	1
TECRL	ENST00000507440.5	c.234+4714T>C		intron_variant	Intron 1 of 11	5		ENSP00000426043.1
TECRL	ENST00000509536.1	c.234+4714T>C		intron_variant	Intron 1 of 3	4		ENSP00000422497.1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39882 AN: 151752 Hom.: 5487 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.263 AC: 39910 AN: 151872 Hom.: 5495 Cov.: 32 AF XY: 0.268 AC XY: 19912 AN XY: 74240

African (AFR) AF: 0.314 AC: 13019 AN: 41442

American (AMR) AF: 0.290 AC: 4416 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1264 AN: 3468

East Asian (EAS) AF: 0.319 AC: 1652 AN: 5174

South Asian (SAS) AF: 0.311 AC: 1497 AN: 4820

European-Finnish (FIN) AF: 0.278 AC: 2924 AN: 10532

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14316 AN: 67884

Other (OTH) AF: 0.276 AC: 581 AN: 2106

Alfa AF: 0.234 Hom.: 2528

Bravo AF: 0.266

Asia WGS AF: 0.307 AC: 1059 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.9
DANN	Benign	0.80
PhyloP100		0.57
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: rs10517893; hg19: chr4-65270122;