chr6-90062093-G-A

Variant names:

• chr6-90062093-G-A
• rs9342220
• NM_021813.4:c.-13+26868C>T

Variant summary

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

The NM_021813.4(BACH2):​c.-13+26868C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,158 control chromosomes in the GnomAD database, including 2,919 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 0.15 (2919 hom., cov: 32)
• Consequence: BACH2 NM_021813.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• Publications: 1 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 (EAS) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BACH2	NM_021813.4	c.-13+26868C>T		intron_variant	Intron 5 of 8	ENST00000257749.9	NP_068585.1
BACH2	NM_001170794.2	c.-13+26868C>T		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.-13+26868C>T		intron_variant	Intron 5 of 8	1	NM_021813.4	ENSP00000257749.4

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22300 AN: 152040 Hom.: 2919 Cov.: 32

Gnomad AFR AF: 0.0314

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.147 AC: 22310 AN: 152158 Hom.: 2919 Cov.: 32 AF XY: 0.157 AC XY: 11664 AN XY: 74366

African (AFR) AF: 0.0313 AC: 1301 AN: 41542

American (AMR) AF: 0.173 AC: 2640 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 495 AN: 3472

East Asian (EAS) AF: 0.679 AC: 3509 AN: 5166

South Asian (SAS) AF: 0.366 AC: 1761 AN: 4816

European-Finnish (FIN) AF: 0.224 AC: 2368 AN: 10568

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.143 AC: 9718 AN: 67998

Other (OTH) AF: 0.137 AC: 290 AN: 2112

Alfa AF: 0.128 Hom.: 1096

Bravo AF: 0.138

Asia WGS AF: 0.489 AC: 1700 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	2.5
DANN	Benign	0.73
PhyloP100		-0.11
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: rs9342220; hg19: chr6-90771812;