Genetic Variant ATF6B:c.1424+38G>A (chr6-32117821-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.18

Variant links:

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]

ATF6B links:

ENSG00000284829 (HGNC:):

ENSG00000284829 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
ATF6B	NM_004381.5 link	c.1424+38G>A		intron_variant	Intron 12 of 17	ENST00000375203.8	NP_004372.3	Q99941-1Q6AZW6
ATF6B	NM_001136153.2 link	c.1415+38G>A		intron_variant	Intron 12 of 17		NP_001129625.1	Q99941-2A0A1U9X796

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ATF6B	ENST00000375203.8 link	c.1424+38G>A	intron_variant	Intron 12 of 17	1	NM_004381.5	ENSP00000364349.3	Q99941-1
ATF6B	ENST00000375201.8 link	c.1415+38G>A	intron_variant	Intron 12 of 17	1		ENSP00000364347.4	Q99941-2
ATF6B	ENST00000453203.2 link	c.1424+38G>A	intron_variant	Intron 12 of 17	5		ENSP00000393419.2	H0Y7D7
ENSG00000284829	ENST00000494022.1 link	n.-211G>A	upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0491

AC:

7470

AN:

152068

Hom.:

264

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0368

AC XY:

25503

AN XY:

692910

show subpopulations

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.:

AF XY:

0.0464

AC XY:

3453

AN XY:

74398

show subpopulations

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:

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over