6-89933656-T-C

Variant names:

• chr6-89933656-T-C
• rs292253
• NM_021813.4:c.2044-766A>G

Variant summary

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

The NM_021813.4(BACH2):​c.2044-766A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,880 control chromosomes in the GnomAD database, including 11,522 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 0.39 (11522 hom., cov: 31)
• Consequence: BACH2 NM_021813.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BACH2	NM_021813.4	c.2044-766A>G		intron_variant	Intron 8 of 8	ENST00000257749.9	NP_068585.1
BACH2	NM_001170794.2	c.2044-766A>G		intron_variant	Intron 6 of 6		NP_001164265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BACH2	ENST00000257749.9	c.2044-766A>G		intron_variant	Intron 8 of 8	1	NM_021813.4	ENSP00000257749.4

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58585 AN: 151764 Hom.: 11515 Cov.: 31

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.386 AC: 58609 AN: 151880 Hom.: 11522 Cov.: 31 AF XY: 0.391 AC XY: 29040 AN XY: 74202

African (AFR) AF: 0.388 AC: 16054 AN: 41392

American (AMR) AF: 0.420 AC: 6412 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1687 AN: 3466

East Asian (EAS) AF: 0.408 AC: 2105 AN: 5154

South Asian (SAS) AF: 0.298 AC: 1435 AN: 4812

European-Finnish (FIN) AF: 0.482 AC: 5072 AN: 10522

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24602 AN: 67952

Other (OTH) AF: 0.399 AC: 843 AN: 2114

Alfa AF: 0.367 Hom.: 5478

Bravo AF: 0.382

Asia WGS AF: 0.352 AC: 1223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.7
DANN	Benign	0.84
PhyloP100		-0.14
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: rs292253; hg19: chr6-90643375;