NM_021813.4:c.-12-14762A>C

Variant names:

• chr6-90023618-T-G
• rs9444730
• NM_021813.4:c.-12-14762A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.86).
• 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 rank	MANE	Protein	UniProt
BACH2	NM_021813.4	c.-12-14762A>C		intron_variant	Intron 5 of 8	ENST00000257749.9	NP_068585.1
BACH2	NM_001170794.2	c.-12-14762A>C		intron_variant	Intron 3 of 6		NP_001164265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BACH2	ENST00000257749.9	c.-12-14762A>C		intron_variant	Intron 5 of 8	1	NM_021813.4	ENSP00000257749.4

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

African (AFR) AF: 0.525 AC: 21754 AN: 41462

American (AMR) AF: 0.361 AC: 5516 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 524 AN: 3470

East Asian (EAS) AF: 0.190 AC: 980 AN: 5166

South Asian (SAS) AF: 0.117 AC: 566 AN: 4820

European-Finnish (FIN) AF: 0.236 AC: 2494 AN: 10590

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14365 AN: 67994

Other (OTH) AF: 0.302 AC: 637 AN: 2110

Alfa AF: 0.197 Hom.: 629

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
PhyloP100		0.87
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: rs9444730; hg19: chr6-90733337;