19-14545053-T-C

Variant names:

• chr19-14545053-T-C
• rs7252966
• NM_138501.6:c.15+15342T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138501.6(TECR):​c.15+15342T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 455,894 control chromosomes in the GnomAD database, including 84,018 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 0.57 (25151 hom., cov: 32)
  • Exomes 𝑓: 0.62 (58867 hom.)
• Consequence: TECR NM_138501.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.90
• Publications: 12 publications found

Genes affected

TECR (HGNC:4551): (trans-2,3-enoyl-CoA reductase) This gene encodes a multi-pass membrane protein that resides in the endoplasmic reticulum, and belongs to the steroid 5-alpha reductase family. The elongation of microsomal long and very long chain fatty acid consists of 4 sequential reactions. This protein catalyzes the final step, reducing trans-2,3-enoyl-CoA to saturated acyl-CoA. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Apr 2011]

DNAJB1 (HGNC:5270): (DnaJ heat shock protein family (Hsp40) member B1) This gene encodes a member of the DnaJ or Hsp40 (heat shock protein 40 kD) family of proteins. DNAJ family members are characterized by a highly conserved amino acid stretch called the 'J-domain' and function as one of the two major classes of molecular chaperones involved in a wide range of cellular events, such as protein folding and oligomeric protein complex assembly. The encoded protein is a molecular chaperone that stimulates the ATPase activity of Hsp70 heat-shock proteins in order to promote protein folding and prevent misfolded protein aggregation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECR	NM_138501.6	c.15+15342T>C		intron_variant	Intron 1 of 12	ENST00000215567.10	NP_612510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TECR	ENST00000215567.10	c.15+15342T>C		intron_variant	Intron 1 of 12	1	NM_138501.6	ENSP00000215567.4

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85861 AN: 151810 Hom.: 25119 Cov.: 32

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.567

GnomAD4 exome AF: 0.616 AC: 187313 AN: 303964 Hom.: 58867 AF XY: 0.625 AC XY: 108190 AN XY: 173076

African (AFR) AF: 0.456 AC: 3929 AN: 8616

American (AMR) AF: 0.495 AC: 13476 AN: 27236

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 8042 AN: 10746

East Asian (EAS) AF: 0.299 AC: 2748 AN: 9202

South Asian (SAS) AF: 0.673 AC: 40207 AN: 59712

European-Finnish (FIN) AF: 0.686 AC: 8779 AN: 12798

Middle Eastern (MID) AF: 0.635 AC: 1767 AN: 2782

European-Non Finnish (NFE) AF: 0.629 AC: 99768 AN: 158646

Other (OTH) AF: 0.604 AC: 8597 AN: 14226

GnomAD4 genome AF: 0.566 AC: 85934 AN: 151930 Hom.: 25151 Cov.: 32 AF XY: 0.568 AC XY: 42188 AN XY: 74264

African (AFR) AF: 0.456 AC: 18892 AN: 41438

American (AMR) AF: 0.511 AC: 7778 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 2581 AN: 3472

East Asian (EAS) AF: 0.296 AC: 1534 AN: 5176

South Asian (SAS) AF: 0.679 AC: 3267 AN: 4814

European-Finnish (FIN) AF: 0.695 AC: 7346 AN: 10574

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42538 AN: 67936

Other (OTH) AF: 0.559 AC: 1173 AN: 2100

Alfa AF: 0.605 Hom.: 88859

Bravo AF: 0.541

Asia WGS AF: 0.477 AC: 1659 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.39
DANN	Benign	0.49
PhyloP100		-2.9
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: rs7252966; hg19: chr19-14655865; COSMIC: COSV53110996; COSMIC: COSV53110996;