chr4-64408122-C-T

Position:

• chr4-64408122-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001010874.5(TECRL):​c.234+996G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0147 in 151,724 control chromosomes in the GnomAD database, including 49 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 0.015 (49 hom., cov: 32)
• Consequence: TECRL NM_001010874.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.48

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=-0.91).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0147 (2229/151724) while in subpopulation AFR AF= 0.0504 (2092/41512). AF 95% confidence interval is 0.0486. There are 49 homozygotes in gnomad4. There are 1045 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TECRL	NM_001010874.5	c.234+996G>A		intron_variant		ENST00000381210.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TECRL	ENST00000381210.8	c.234+996G>A		intron_variant		1	NM_001010874.5	P1
TECRL	ENST00000511356.1	n.339+996G>A		intron_variant, non_coding_transcript_variant		1
TECRL	ENST00000507440.5	c.234+996G>A		intron_variant		5
TECRL	ENST00000509536.1	c.234+996G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 2224 AN: 151610 Hom.: 49 Cov.: 32

Gnomad AFR AF: 0.0504

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00539

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000325

Gnomad OTH AF: 0.0149

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

GnomAD4 genome AF: 0.0147 AC: 2229 AN: 151724 Hom.: 49 Cov.: 32 AF XY: 0.0141 AC XY: 1045 AN XY: 74148

Gnomad4 AFR AF: 0.0504

Gnomad4 AMR AF: 0.00539

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000325

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00279 Hom.: 1

Bravo AF: 0.0169

Asia WGS AF: 0.00410 AC: 14 AN: 3426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0080
DANN	Benign	0.34

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: rs6836944; hg19: chr4-65273840;