chr22-41381096-G-T

Position:

• chr22-41381096-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_938271.3(LOC105373042):​n.172+644C>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 152,126 control chromosomes in the GnomAD database, including 44,631 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 0.76 (44631 hom., cov: 32)
• Consequence: LOC105373042 XR_938271.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.432

Genes affected

LOC105373042 (HGNC:):

TEF (HGNC:11722): (TEF transcription factor, PAR bZIP family member) This gene encodes a member of the PAR (proline and acidic amino acid-rich) subfamily of basic region/leucine zipper (bZIP) transcription factors. It is expressed in a broad range of cells and tissues in adult animals, however, during embryonic development, TEF expression appears to be restricted to the developing anterior pituitary gland, coincident with the appearance of thyroid-stimulating hormone, beta (TSHB). Indeed, TEF can bind to, and transactivate the TSHB promoter. It shows homology (in the functional domains) with other members of the PAR-bZIP subfamily of transcription factors, which include albumin D box-binding protein (DBP), human hepatic leukemia factor (HLF) and chicken vitellogenin gene-binding protein (VBP); VBP is considered the chicken homologue of TEF. Different members of the subfamily can readily form heterodimers, and share DNA-binding, and transcriptional regulatory properties. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105373042	XR_938271.3	n.172+644C>A		intron_variant, non_coding_transcript_variant
TEF	NM_001145398.3	c.68-6255G>T		intron_variant			NP_001138870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEF	ENST00000406644.7	c.68-6255G>T		intron_variant		2		ENSP00000385256

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115788 AN: 152008 Hom.: 44579 Cov.: 32

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.805

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.723

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.740

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

GnomAD4 genome AF: 0.762 AC: 115894 AN: 152126 Hom.: 44631 Cov.: 32 AF XY: 0.764 AC XY: 56853 AN XY: 74374

Gnomad4 AFR AF: 0.854

Gnomad4 AMR AF: 0.811

Gnomad4 ASJ AF: 0.770

Gnomad4 EAS AF: 0.805

Gnomad4 SAS AF: 0.755

Gnomad4 FIN AF: 0.693

Gnomad4 NFE AF: 0.703

Gnomad4 OTH AF: 0.732

Alfa AF: 0.718 Hom.: 45834

Bravo AF: 0.775

Asia WGS AF: 0.710 AC: 2472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.87

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs738499; hg19: chr22-41777100;