4-64279745-G-T

Position:

• chr4-64279745-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001010874.5(TECRL):​c.*327C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.973 in 981,498 control chromosomes in the GnomAD database, including 465,148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.97 (71181 hom., cov: 31)
  • Exomes 𝑓: 0.97 (393967 hom.)
• Consequence: TECRL NM_001010874.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.878

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BP6: Variant 4-64279745-G-T is Benign according to our data. Variant chr4-64279745-G-T is described in ClinVar as [Benign]. Clinvar id is 1296724.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.*327C>A		3_prime_UTR_variant	12/12	ENST00000381210.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TECRL	ENST00000381210.8	c.*327C>A		3_prime_UTR_variant	12/12	1	NM_001010874.5	P1
TECRL	ENST00000507440.5	c.964+1296C>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.968 AC: 147025 AN: 151960 Hom.: 71147 Cov.: 31

Gnomad AFR AF: 0.945

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.978

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: 0.965

GnomAD4 exome AF: 0.975 AC: 808355 AN: 829420 Hom.: 393967 Cov.: 17 AF XY: 0.974 AC XY: 373880 AN XY: 383672

Gnomad4 AFR exome AF: 0.945

Gnomad4 AMR exome AF: 0.984

Gnomad4 ASJ exome AF: 0.966

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.989

Gnomad4 FIN exome AF: 0.989

Gnomad4 NFE exome AF: 0.975

Gnomad4 OTH exome AF: 0.976

GnomAD4 genome AF: 0.967 AC: 147118 AN: 152078 Hom.: 71181 Cov.: 31 AF XY: 0.968 AC XY: 71972 AN XY: 74360

Gnomad4 AFR AF: 0.945

Gnomad4 AMR AF: 0.978

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: 0.965

Alfa AF: 0.972 Hom.: 9751

Bravo AF: 0.966

Asia WGS AF: 0.984 AC: 3416 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.55
DANN	Benign	0.32

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: rs2348313; hg19: chr4-65145463;