4-64404404-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TECRL	NM_001010874.5	c.234+4714T>C		intron_variant		ENST00000381210.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TECRL	ENST00000381210.8	c.234+4714T>C		intron_variant		1	NM_001010874.5	P1
TECRL	ENST00000511356.1	n.339+4714T>C		intron_variant, non_coding_transcript_variant		1
TECRL	ENST00000507440.5	c.234+4714T>C		intron_variant		5
TECRL	ENST00000509536.1	c.234+4714T>C		intron_variant		4

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

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.319

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.276

Alfa AF: 0.233 Hom.: 2262

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs10517893; hg19: chr4-65270122;