rs12204127

Variant names:

• chr6-89988555-C-T
• rs12204127
• NM_021813.4:c.243+20047G>A

Variant summary

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

The NM_021813.4(BACH2):​c.243+20047G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,044 control chromosomes in the GnomAD database, including 2,389 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 (2389 hom., cov: 32)
• Consequence: BACH2 NM_021813.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• Publications: 4 publications found

Genes affected

BACH2 (HGNC:14078): (BTB domain and CNC homolog 2) Enables sequence-specific double-stranded DNA binding activity. Involved in primary adaptive immune response involving T cells and B cells. Located in cytosol and nucleoplasm. Implicated in immunodeficiency 60. [provided by Alliance of Genome Resources, Apr 2022]

BACH2 Gene-Disease associations (from GenCC):

• immunodeficiency 60

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Illumina, ClinGen, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BACH2	NM_021813.4	c.243+20047G>A		intron_variant	Intron 6 of 8	ENST00000257749.9	NP_068585.1
BACH2	NM_001170794.2	c.243+20047G>A		intron_variant	Intron 4 of 6		NP_001164265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BACH2	ENST00000257749.9	c.243+20047G>A		intron_variant	Intron 6 of 8	1	NM_021813.4	ENSP00000257749.4

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24082 AN: 151926 Hom.: 2387 Cov.: 32

Gnomad AFR AF: 0.0559

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0462

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.158 AC: 24085 AN: 152044 Hom.: 2389 Cov.: 32 AF XY: 0.157 AC XY: 11661 AN XY: 74320

African (AFR) AF: 0.0561 AC: 2329 AN: 41486

American (AMR) AF: 0.126 AC: 1926 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 737 AN: 3470

East Asian (EAS) AF: 0.0459 AC: 238 AN: 5180

South Asian (SAS) AF: 0.154 AC: 738 AN: 4802

European-Finnish (FIN) AF: 0.211 AC: 2220 AN: 10538

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15315 AN: 67978

Other (OTH) AF: 0.179 AC: 378 AN: 2114

Alfa AF: 0.199 Hom.: 9480

Bravo AF: 0.147

Asia WGS AF: 0.103 AC: 357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.5
DANN	Benign	0.34
PhyloP100		-0.066
Mutation Taster		=100/0	polymorphism (auto)

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: rs12204127; hg19: chr6-90698274;