chr4-64304697-C-A

Position:

• chr4-64304697-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001010874.5(TECRL):​c.730+469G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 151,820 control chromosomes in the GnomAD database, including 3,520 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 0.21 (3520 hom., cov: 32)
• Consequence: TECRL NM_001010874.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TECRL	NM_001010874.5	c.730+469G>T		intron_variant		ENST00000381210.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TECRL	ENST00000381210.8	c.730+469G>T		intron_variant		1	NM_001010874.5	P1
TECRL	ENST00000507440.5	c.730+469G>T		intron_variant		5
TECRL	ENST00000513125.5	n.303+469G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.211 AC: 31958 AN: 151702 Hom.: 3518 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.211 AC: 31971 AN: 151820 Hom.: 3520 Cov.: 32 AF XY: 0.215 AC XY: 15939 AN XY: 74184

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.215

Alfa AF: 0.201 Hom.: 5378

Bravo AF: 0.211

Asia WGS AF: 0.274 AC: 947 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.42
DANN	Benign	0.58

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: rs7656244; hg19: chr4-65170415;