rs2832283

Variant names:

• chr21-29318237-G-A
• rs2832283
• NM_001186.4:c.-60-2984G>A

Variant summary

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

The NM_001186.4(BACH1):​c.-60-2984G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,222 control chromosomes in the GnomAD database, including 2,573 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 0.16 (2573 hom., cov: 32)
• Consequence: BACH1 NM_001186.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250
• Publications: 14 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BACH1	NM_001186.4	c.-60-2984G>A		intron_variant	Intron 1 of 4	ENST00000286800.8	NP_001177.1
BACH1	NM_206866.3	c.-60-2984G>A		intron_variant	Intron 1 of 4		NP_996749.1
BACH1	NR_027655.3	n.120-2984G>A		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BACH1	ENST00000286800.8	c.-60-2984G>A		intron_variant	Intron 1 of 4	1	NM_001186.4	ENSP00000286800.3

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24441 AN: 152104 Hom.: 2576 Cov.: 32

Gnomad AFR AF: 0.0387

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.0548

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.161 AC: 24436 AN: 152222 Hom.: 2573 Cov.: 32 AF XY: 0.163 AC XY: 12147 AN XY: 74422

African (AFR) AF: 0.0385 AC: 1602 AN: 41570

American (AMR) AF: 0.138 AC: 2117 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 701 AN: 3468

East Asian (EAS) AF: 0.0551 AC: 286 AN: 5188

South Asian (SAS) AF: 0.258 AC: 1243 AN: 4814

European-Finnish (FIN) AF: 0.267 AC: 2825 AN: 10590

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15162 AN: 67982

Other (OTH) AF: 0.173 AC: 364 AN: 2110

Alfa AF: 0.202 Hom.: 5725

Bravo AF: 0.142

Asia WGS AF: 0.163 AC: 570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	13
DANN	Benign	0.77
PhyloP100		-0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2832283; hg19: chr21-30690558;