NM_001010874.5:c.730+469G>T

Variant names:

• chr4-64304697-C-A
• rs7656244
• NM_001010874.5:c.730+469G>T

Variant summary

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010874.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECRL	NM_001010874.5	MANE Select	c.730+469G>T		intron	N/A	NP_001010874.2
	TECRL	NM_001363796.1		c.730+469G>T		intron	N/A	NP_001350725.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECRL	ENST00000381210.8	TSL:1 MANE Select	c.730+469G>T		intron	N/A	ENSP00000370607.3
	TECRL	ENST00000941916.1		c.955+469G>T		intron	N/A	ENSP00000611975.1
	TECRL	ENST00000941915.1		c.799+469G>T		intron	N/A	ENSP00000611974.1

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

African (AFR) AF: 0.222 AC: 9187 AN: 41420

American (AMR) AF: 0.221 AC: 3359 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1045 AN: 3466

East Asian (EAS) AF: 0.277 AC: 1429 AN: 5166

South Asian (SAS) AF: 0.277 AC: 1335 AN: 4820

European-Finnish (FIN) AF: 0.207 AC: 2175 AN: 10524

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12780 AN: 67892

Other (OTH) AF: 0.215 AC: 454 AN: 2112

Alfa AF: 0.200 Hom.: 11186

Bravo AF: 0.211

Asia WGS AF: 0.274 AC: 947 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.42
DANN	Benign	0.58
PhyloP100		-1.6
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: rs7656244; hg19: chr4-65170415;