rs2474619

Variant names:

• chr6-90170316-C-A
• rs2474619
• NM_021813.4:c.-162+36253G>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.-162+36253G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 152,088 control chromosomes in the GnomAD database, including 40,939 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 0.72 (40939 hom., cov: 32)
• Consequence: BACH2 NM_021813.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.660
• Publications: 17 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BACH2	NM_021813.4	c.-162+36253G>T		intron_variant	Intron 4 of 8	ENST00000257749.9	NP_068585.1
BACH2	NM_001170794.2	c.-162+36253G>T		intron_variant	Intron 2 of 6		NP_001164265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BACH2	ENST00000257749.9	c.-162+36253G>T		intron_variant	Intron 4 of 8	1	NM_021813.4	ENSP00000257749.4

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109237 AN: 151970 Hom.: 40869 Cov.: 32

Gnomad AFR AF: 0.932

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.723

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.738

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

GnomAD4 genome AF: 0.719 AC: 109371 AN: 152088 Hom.: 40939 Cov.: 32 AF XY: 0.716 AC XY: 53226 AN XY: 74336

African (AFR) AF: 0.933 AC: 38765 AN: 41562

American (AMR) AF: 0.746 AC: 11387 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2447 AN: 3470

East Asian (EAS) AF: 0.600 AC: 3093 AN: 5158

South Asian (SAS) AF: 0.748 AC: 3600 AN: 4814

European-Finnish (FIN) AF: 0.501 AC: 5291 AN: 10554

Middle Eastern (MID) AF: 0.726 AC: 212 AN: 292

European-Non Finnish (NFE) AF: 0.624 AC: 42400 AN: 67954

Other (OTH) AF: 0.740 AC: 1562 AN: 2112

Alfa AF: 0.650 Hom.: 62231

Bravo AF: 0.746

Asia WGS AF: 0.716 AC: 2491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.32
DANN	Benign	0.47
PhyloP100		-0.66
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: rs2474619; hg19: chr6-90880035;