4-64280993-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001010874.5(TECRL):c.964+48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.975 in 1,403,786 control chromosomes in the GnomAD database, including 666,972 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.97 (71215 hom., cov: 32)
  • Exomes 𝑓: 0.98 (595757 hom.)
• Consequence: TECRL NM_001010874.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.42

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 4-64280993-T-C is Benign according to our data. Variant chr4-64280993-T-C is described in ClinVar as [Benign]. Clinvar id is 1240736.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TECRL	NM_001010874.5	c.964+48A>G		intron_variant		ENST00000381210.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TECRL	ENST00000381210.8	c.964+48A>G		intron_variant		1	NM_001010874.5	P1
TECRL	ENST00000511997.1	c.63+481A>G		intron_variant		1
TECRL	ENST00000507440.5	c.964+48A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.968 AC: 147051 AN: 151944 Hom.: 71181 Cov.: 32

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.917

Gnomad AMR AF: 0.979

Gnomad ASJ AF: 0.965

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.989

Gnomad FIN AF: 0.988

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.972

Gnomad OTH AF: 0.966

GnomAD3 exomes AF: 0.978 AC: 226337 AN: 231468 Hom.: 110677 AF XY: 0.979 AC XY: 122922 AN XY: 125598

Gnomad AFR exome AF: 0.947

Gnomad AMR exome AF: 0.986

Gnomad ASJ exome AF: 0.970

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.988

Gnomad FIN exome AF: 0.984

Gnomad NFE exome AF: 0.973

Gnomad OTH exome AF: 0.974

GnomAD4 exome AF: 0.976 AC: 1221171 AN: 1251724 Hom.: 595757 Cov.: 15 AF XY: 0.976 AC XY: 614420 AN XY: 629606

Gnomad4 AFR exome AF: 0.946

Gnomad4 AMR exome AF: 0.984

Gnomad4 ASJ exome AF: 0.967

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.988

Gnomad4 FIN exome AF: 0.984

Gnomad4 NFE exome AF: 0.974

Gnomad4 OTH exome AF: 0.974

GnomAD4 genome AF: 0.968 AC: 147144 AN: 152062 Hom.: 71215 Cov.: 32 AF XY: 0.968 AC XY: 71956 AN XY: 74326

Gnomad4 AFR AF: 0.946

Gnomad4 AMR AF: 0.979

Gnomad4 ASJ AF: 0.965

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.989

Gnomad4 FIN AF: 0.988

Gnomad4 NFE AF: 0.972

Gnomad4 OTH AF: 0.966

Alfa AF: 0.968 Hom.: 13224

Bravo AF: 0.966

Asia WGS AF: 0.986 AC: 3421 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 29, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.64
Dann	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1483709; hg19: chr4-65146711;