6-32115398-C-T

Variant names:

• chr6-32115398-C-T
• rs8111
• NM_004381.5:c.*341G>A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_004381.5(ATF6B):​c.*341G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 136,292 control chromosomes in the GnomAD database, including 5,748 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (4627 hom., cov: 22)
  • Exomes 𝑓: 0.55 (1121 hom.)
• Consequence: ATF6B NM_004381.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATF6B	NM_004381.5	c.*341G>A		3_prime_UTR_variant	Exon 18 of 18	ENST00000375203.8	NP_004372.3
ATF6B	NM_001136153.2	c.*341G>A		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.*341G>A		3_prime_UTR_variant	Exon 18 of 18	1	NM_004381.5	ENSP00000364349.3

Frequencies

GnomAD3 genomes AF: 0.263 AC: 32425 AN: 123342 Hom.: 4623 Cov.: 22

Gnomad AFR AF: 0.0679

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.372

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.275

GnomAD4 exome AF: 0.555 AC: 7150 AN: 12894 Hom.: 1121 Cov.: 0 AF XY: 0.553 AC XY: 3586 AN XY: 6486

Gnomad4 AFR exome AF: 0.359

Gnomad4 AMR exome AF: 0.571

Gnomad4 ASJ exome AF: 0.628

Gnomad4 EAS exome AF: 0.499

Gnomad4 SAS exome AF: 0.480

Gnomad4 FIN exome AF: 0.562

Gnomad4 NFE exome AF: 0.556

Gnomad4 OTH exome AF: 0.555

GnomAD4 genome AF: 0.263 AC: 32439 AN: 123398 Hom.: 4627 Cov.: 22 AF XY: 0.271 AC XY: 16017 AN XY: 59104

Gnomad4 AFR AF: 0.0678

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.278

Alfa AF: 0.281 Hom.: 10901

Bravo AF: 0.210

Asia WGS AF: 0.199 AC: 695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	16
DANN	Benign	0.93
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0

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: rs8111; hg19: chr6-32083175;