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

Variant summary

Our verdict is Benign. The variant received -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

Publications

21 publications found

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 was made for transcript

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

Gene	Transcript	Tags	HGVSc	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.:

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

GnomAD2 exomes

AF:

0.0297

AC:

5218

AN:

175784

AF XY:

0.0273

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 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

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:

AN:

38976

South Asian (SAS)

AF:

0.000416

AC:

AN:

76954

European-Finnish (FIN)

AF:

0.00431

AC:

217

AN:

50392

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

5326

European-Non Finnish (NFE)

AF:

0.0434

AC:

47079

AN:

1084628

Other (OTH)

AF:

0.0376

AC:

2178

AN:

57990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

3158

6316

9475

12633

15791

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1936

3872

5808

7744

9680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0491

AC:

7477

AN:

152186

Hom.:

264

Cov.:

AF XY:

0.0464

AC XY:

3453

AN XY:

74398

show subpopulations

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:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00104

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00264

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0360

AC:

2451

AN:

68002

Other (OTH)

AF:

0.0501

AC:

106

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

350

700

1050

1400

1750

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0375

Hom.:

315

Bravo

AF:

0.0565

Asia WGS

AF:

0.00404

AC:

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

(source)

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over