NM_004381.5:c.-260G>A

Variant names:

• chr6-32128467-C-T
• rs3830076
• NM_004381.5:c.-260G>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.-260G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0589 in 152,146 control chromosomes in the GnomAD database, including 400 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 0.059 (400 hom., cov: 31)
• Consequence: ATF6B NM_004381.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.80
• Publications: 31 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]

FKBPL (HGNC:13949): (FKBP prolyl isomerase like) The protein encoded by this gene has similarity to the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. The encoded protein is thought to have a potential role in the induced radioresistance. Also it appears to have some involvement in the control of the cell cycle. [provided by RefSeq, Jul 2008]

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 (AMR) allele frequency at 95% confidence interval = 0.139 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.-260G>A		upstream_gene	N/A	NP_004372.3
	FKBPL	NM_022110.4	MANE Select	c.*264G>A		downstream_gene	N/A	NP_071393.2
	ATF6B	NM_001136153.2		c.-260G>A		upstream_gene	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.-260G>A		upstream_gene	N/A	ENSP00000364349.3	Q99941-1
	ATF6B	ENST00000375201.8	TSL:1	c.-260G>A		upstream_gene	N/A	ENSP00000364347.4	Q99941-2
	FKBPL	ENST00000375156.4	TSL:1 MANE Select	c.*264G>A		downstream_gene	N/A	ENSP00000364298.3	Q9UIM3

Frequencies

GnomAD3 genomes AF: 0.0588 AC: 8940 AN: 152028 Hom.: 400 Cov.: 31

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.0964

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0608

Gnomad OTH AF: 0.0493

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0589 AC: 8957 AN: 152146 Hom.: 400 Cov.: 31 AF XY: 0.0617 AC XY: 4590 AN XY: 74358

African (AFR) AF: 0.0126 AC: 521 AN: 41512

American (AMR) AF: 0.144 AC: 2195 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3472

East Asian (EAS) AF: 0.0968 AC: 501 AN: 5174

South Asian (SAS) AF: 0.0172 AC: 83 AN: 4824

European-Finnish (FIN) AF: 0.127 AC: 1344 AN: 10568

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0607 AC: 4131 AN: 68000

Other (OTH) AF: 0.0507 AC: 107 AN: 2110

Alfa AF: 0.0650 Hom.: 988

Bravo AF: 0.0598

Asia WGS AF: 0.0680 AC: 238 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	0.021
DANN	Benign	0.81
PhyloP100		-2.8
PromoterAI		-0.061	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3830076; hg19: chr6-32096244;