6-90023618-T-G

Variant summary

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

The NM_021813.4(BACH2):c.-12-14762A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,084 control chromosomes in the GnomAD database, including 8,865 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 0.31 (8865 hom., cov: 32)
• Consequence: BACH2 NM_021813.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.873

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BACH2	NM_021813.4	c.-12-14762A>C		intron_variant		ENST00000257749.9
BACH2	NM_001170794.2	c.-12-14762A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BACH2	ENST00000257749.9	c.-12-14762A>C		intron_variant		1	NM_021813.4	P1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 47005 AN: 151966 Hom.: 8852 Cov.: 32

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.309 AC: 47056 AN: 152084 Hom.: 8865 Cov.: 32 AF XY: 0.308 AC XY: 22929 AN XY: 74340

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.302

Alfa AF: 0.184 Hom.: 529

Bravo AF: 0.332

Asia WGS AF: 0.183 AC: 636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	13
Dann	Benign	0.78

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: rs9444730; hg19: chr6-90733337;