rs12212193

Positions:

• chr6-90287050-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021813.4(BACH2):​c.-446+9430T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 151,996 control chromosomes in the GnomAD database, including 11,827 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 0.38 (11827 hom., cov: 31)
• Consequence: BACH2 NM_021813.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BACH2	NM_021813.4	c.-446+9430T>C		intron_variant		ENST00000257749.9	NP_068585.1
BACH2	NM_001170794.2	c.-275+9430T>C		intron_variant			NP_001164265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BACH2	ENST00000257749.9	c.-446+9430T>C		intron_variant		1	NM_021813.4	ENSP00000257749	P1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58095 AN: 151878 Hom.: 11803 Cov.: 31

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.0486

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.383 AC: 58147 AN: 151996 Hom.: 11827 Cov.: 31 AF XY: 0.374 AC XY: 27773 AN XY: 74310

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.0489

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.386

Alfa AF: 0.439 Hom.: 18105

Bravo AF: 0.381

Asia WGS AF: 0.234 AC: 816 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	3.3
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs12212193; hg19: chr6-90996769; COSMIC: COSV57606730;