rs204890

chr6-32117821-C-T

Variant summary

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

The NM_004381.5(ATF6B):c.1424+38G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0397 in 1,555,400 control chromosomes in the GnomAD database, including 1,570 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 0.049 (264 hom., cov: 32)
  • Exomes 𝑓: 0.039 (1306 hom.)
• Consequence: ATF6B NM_004381.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATF6B	NM_004381.5	c.1424+38G>A		intron_variant		ENST00000375203.8
ATF6B	NM_001136153.2	c.1415+38G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATF6B	ENST00000375203.8	c.1424+38G>A		intron_variant		1	NM_004381.5	A2
ATF6B	ENST00000375201.8	c.1415+38G>A		intron_variant		1		P4
ATF6B	ENST00000453203.2	c.1424+38G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0491 AC: 7470 AN: 152068 Hom.: 264 Cov.: 32

Gnomad AFR AF: 0.0971

Gnomad AMI AF: 0.0198

Gnomad AMR AF: 0.0513

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00264

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0360

Gnomad OTH AF: 0.0507

GnomAD3 exomes AF: 0.0297 AC: 5218 AN: 175784 Hom.: 144 AF XY: 0.0273 AC XY: 2544 AN XY: 93202

Gnomad AFR exome AF: 0.0974

Gnomad AMR exome AF: 0.0393

Gnomad ASJ exome AF: 0.0156

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000254

Gnomad FIN exome AF: 0.00378

Gnomad NFE exome AF: 0.0352

Gnomad OTH exome AF: 0.0381

GnomAD4 exome AF: 0.0387 AC: 54328 AN: 1403214 Hom.: 1306 Cov.: 33 AF XY: 0.0368 AC XY: 25503 AN XY: 692910

Gnomad4 AFR exome AF: 0.0949

Gnomad4 AMR exome AF: 0.0404

Gnomad4 ASJ exome AF: 0.0150

Gnomad4 EAS exome AF: 0.0000513

Gnomad4 SAS exome AF: 0.000416

Gnomad4 FIN exome AF: 0.00431

Gnomad4 NFE exome AF: 0.0434

Gnomad4 OTH exome AF: 0.0376

GnomAD4 genome AF: 0.0491 AC: 7477 AN: 152186 Hom.: 264 Cov.: 32 AF XY: 0.0464 AC XY: 3453 AN XY: 74398

Gnomad4 AFR AF: 0.0969

Gnomad4 AMR AF: 0.0513

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00264

Gnomad4 NFE AF: 0.0360

Gnomad4 OTH AF: 0.0501

Alfa AF: 0.0317 Hom.: 102

Bravo AF: 0.0565

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.39
Dann	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs204890; hg19: chr6-32085598;