chr21-29491574-A-G

Variant names:

• chr21-29491574-A-G
• rs2832357
• ENST00000422809.5:c.472-90738A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000422809.5(BACH1):​c.472-90738A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,174 control chromosomes in the GnomAD database, including 2,226 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 0.12 (2226 hom., cov: 33)
• Consequence: BACH1 ENST00000422809.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.187
• Publications: 2 publications found

Genes affected

BACH1 (HGNC:935): (BTB domain and CNC homolog 1) This gene encodes a transcription factor that belongs to the cap'n'collar type of basic region leucine zipper factor family (CNC-bZip). The encoded protein contains broad complex, tramtrack, bric-a-brac/poxvirus and zinc finger (BTB/POZ) domains, which is atypical of CNC-bZip family members. These BTB/POZ domains facilitate protein-protein interactions and formation of homo- and/or hetero-oligomers. When this encoded protein forms a heterodimer with MafK, it functions as a repressor of Maf recognition element (MARE) and transcription is repressed. Multiple alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, May 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BACH1	ENST00000422809.5	c.472-90738A>G		intron_variant	Intron 2 of 4	5		ENSP00000416569.1
BACH1	ENST00000468059.1	c.325-105996A>G		intron_variant	Intron 2 of 3	3		ENSP00000470673.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17807 AN: 152056 Hom.: 2209 Cov.: 33

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0283

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.0410

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.0279

Gnomad OTH AF: 0.0930

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

GnomAD4 genome AF: 0.118 AC: 17885 AN: 152174 Hom.: 2226 Cov.: 33 AF XY: 0.117 AC XY: 8704 AN XY: 74402

African (AFR) AF: 0.308 AC: 12771 AN: 41490

American (AMR) AF: 0.101 AC: 1543 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0283 AC: 98 AN: 3468

East Asian (EAS) AF: 0.158 AC: 815 AN: 5172

South Asian (SAS) AF: 0.0414 AC: 200 AN: 4828

European-Finnish (FIN) AF: 0.0311 AC: 330 AN: 10598

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.0279 AC: 1897 AN: 68008

Other (OTH) AF: 0.0963 AC: 203 AN: 2108

Alfa AF: 0.0555 Hom.: 327

Bravo AF: 0.132

Asia WGS AF: 0.139 AC: 483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.7
DANN	Benign	0.89
PhyloP100		0.19

Splicing

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

Other links and lift over

dbSNP: rs2832357; hg19: chr21-30863894;