4-64280982-A-G

Position:

• chr4-64280982-A-G

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.964+59T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.939 in 1,280,848 control chromosomes in the GnomAD database, including 569,650 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (57579 hom., cov: 32)
  • Exomes 𝑓: 0.95 (512071 hom.)
• Consequence: TECRL NM_001010874.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.287

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=-0.88).
• BP6: Variant 4-64280982-A-G is Benign according to our data. Variant chr4-64280982-A-G is described in ClinVar as [Benign]. Clinvar id is 1221036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TECRL	NM_001010874.5	c.964+59T>C		intron_variant		ENST00000381210.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TECRL	ENST00000381210.8	c.964+59T>C		intron_variant		1	NM_001010874.5	P1
TECRL	ENST00000511997.1	c.63+492T>C		intron_variant		1
TECRL	ENST00000507440.5	c.964+59T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.855 AC: 129842 AN: 151888 Hom.: 57580 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.917

Gnomad AMR AF: 0.923

Gnomad ASJ AF: 0.932

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.968

Gnomad FIN AF: 0.986

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.956

Gnomad OTH AF: 0.870

GnomAD4 exome AF: 0.950 AC: 1072867 AN: 1128842 Hom.: 512071 AF XY: 0.952 AC XY: 543941 AN XY: 571074

Gnomad4 AFR exome AF: 0.572

Gnomad4 AMR exome AF: 0.953

Gnomad4 ASJ exome AF: 0.932

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.972

Gnomad4 FIN exome AF: 0.981

Gnomad4 NFE exome AF: 0.958

Gnomad4 OTH exome AF: 0.930

GnomAD4 genome AF: 0.854 AC: 129870 AN: 152006 Hom.: 57579 Cov.: 32 AF XY: 0.860 AC XY: 63873 AN XY: 74302

Gnomad4 AFR AF: 0.588

Gnomad4 AMR AF: 0.924

Gnomad4 ASJ AF: 0.932

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.968

Gnomad4 FIN AF: 0.986

Gnomad4 NFE AF: 0.956

Gnomad4 OTH AF: 0.869

Alfa AF: 0.891 Hom.: 5361

Bravo AF: 0.838

Asia WGS AF: 0.948 AC: 3294 AN: 3476

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	-0.88
CADD	Benign	1.2
DANN	Benign	0.57

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: rs10012755; hg19: chr4-65146700;