6-32115523-A-G

Variant names:

• chr6-32115523-A-G
• rs8283
• NM_004381.5:c.*216T>C

Variant summary

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

The NM_004381.5(ATF6B):​c.*216T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 448,564 control chromosomes in the GnomAD database, including 13,151 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 0.26 (5847 hom., cov: 31)
  • Exomes 𝑓: 0.21 (7304 hom.)
• Consequence: ATF6B NM_004381.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254

Genes affected

ATF6B (HGNC:2349): (activating transcription factor 6 beta) The protein encoded by this gene is a transcription factor in the unfolded protein response (UPR) pathway during ER stress. Either as a homodimer or as a heterodimer with ATF6-alpha, the encoded protein binds to the ER stress response element, interacting with nuclear transcription factor Y to activate UPR target genes. The protein is normally found in the membrane of the endoplasmic reticulum; however, under ER stress, the N-terminal cytoplasmic domain is cleaved from the rest of the protein and translocates to the nucleus. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

ENSG00000284829 (HGNC:):

TNXB (HGNC:11976): (tenascin XB) This gene encodes a member of the tenascin family of extracellular matrix glycoproteins. The tenascins have anti-adhesive effects, as opposed to fibronectin which is adhesive. This protein is thought to function in matrix maturation during wound healing, and its deficiency has been associated with the connective tissue disorder Ehlers-Danlos syndrome. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. It is one of four genes in this cluster which have been duplicated. The duplicated copy of this gene is incomplete and is a pseudogene which is transcribed but does not encode a protein. The structure of this gene is unusual in that it overlaps the CREBL1 and CYP21A2 genes at its 5' and 3' ends, respectively. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATF6B	NM_004381.5	c.*216T>C		3_prime_UTR_variant	Exon 18 of 18	ENST00000375203.8	NP_004372.3
ATF6B	NM_001136153.2	c.*216T>C		3_prime_UTR_variant	Exon 18 of 18		NP_001129625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATF6B	ENST00000375203	c.*216T>C		3_prime_UTR_variant	Exon 18 of 18	1	NM_004381.5	ENSP00000364349.3

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38977 AN: 151898 Hom.: 5844 Cov.: 31

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.282

GnomAD4 exome AF: 0.206 AC: 60980 AN: 296548 Hom.: 7304 Cov.: 3 AF XY: 0.208 AC XY: 31412 AN XY: 151122

Gnomad4 AFR exome AF: 0.386

Gnomad4 AMR exome AF: 0.183

Gnomad4 ASJ exome AF: 0.207

Gnomad4 EAS exome AF: 0.275

Gnomad4 SAS exome AF: 0.450

Gnomad4 FIN exome AF: 0.141

Gnomad4 NFE exome AF: 0.184

Gnomad4 OTH exome AF: 0.218

GnomAD4 genome AF: 0.257 AC: 39011 AN: 152016 Hom.: 5847 Cov.: 31 AF XY: 0.260 AC XY: 19310 AN XY: 74344

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.279

Alfa AF: 0.204 Hom.: 5106

Bravo AF: 0.264

Asia WGS AF: 0.387 AC: 1346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.6
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8283; hg19: chr6-32083300;