chr6-32117821-C-T

Variant names:

• chr6-32117821-C-T
• rs204890
• NM_004381.5:c.1424+38G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 publications found

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:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004381.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF6B	NM_004381.5	MANE Select	c.1424+38G>A		intron	N/A	NP_004372.3
	ATF6B	NM_001136153.2		c.1415+38G>A		intron	N/A	NP_001129625.1	Q99941-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF6B	ENST00000375203.8	TSL:1 MANE Select	c.1424+38G>A		intron	N/A	ENSP00000364349.3	Q99941-1
	ATF6B	ENST00000375201.8	TSL:1	c.1415+38G>A		intron	N/A	ENSP00000364347.4	Q99941-2
	ATF6B	ENST00000932422.1		c.1436+38G>A		intron	N/A	ENSP00000602481.1

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

GnomAD2 exomes AF: 0.0297 AC: 5218 AN: 175784 AF XY: 0.0273

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 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

African (AFR) AF: 0.0949 AC: 3040 AN: 32040

American (AMR) AF: 0.0404 AC: 1386 AN: 34334

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 339 AN: 22574

East Asian (EAS) AF: 0.0000513 AC: 2 AN: 38976

South Asian (SAS) AF: 0.000416 AC: 32 AN: 76954

European-Finnish (FIN) AF: 0.00431 AC: 217 AN: 50392

Middle Eastern (MID) AF: 0.0103 AC: 55 AN: 5326

European-Non Finnish (NFE) AF: 0.0434 AC: 47079 AN: 1084628

Other (OTH) AF: 0.0376 AC: 2178 AN: 57990

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

African (AFR) AF: 0.0969 AC: 4024 AN: 41506

American (AMR) AF: 0.0513 AC: 784 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 52 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4822

European-Finnish (FIN) AF: 0.00264 AC: 28 AN: 10594

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0360 AC: 2451 AN: 68002

Other (OTH) AF: 0.0501 AC: 106 AN: 2114

Alfa AF: 0.0375 Hom.: 315

Bravo AF: 0.0565

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.39
DANN	Benign	0.76
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs204890; hg19: chr6-32085598;