rs8111

Positions:

• chr6-32115398-C-T

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]

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/exons	MANE	UniProt
ATF6B	NM_004381.5	c.*341G>A		3_prime_UTR_variant	18/18	ENST00000375203.8
ATF6B	NM_001136153.2	c.*341G>A		3_prime_UTR_variant	18/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATF6B	ENST00000375203.8	c.*341G>A		3_prime_UTR_variant	18/18	1	NM_004381.5	A2
ATF6B	ENST00000375201.8	c.*341G>A		3_prime_UTR_variant	18/18	1		P4
ATF6B	ENST00000453203.2	c.*592G>A		3_prime_UTR_variant	18/18	5

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;