6-90212021-C-A

Variant names:

• chr6-90212021-C-A
• rs370409
• NM_021813.4:c.-274-5340G>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.-274-5340G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,046 control chromosomes in the GnomAD database, including 45,011 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 0.76 (45011 hom., cov: 32)
• Consequence: BACH2 NM_021813.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133
• Publications: 16 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BACH2	NM_021813.4	c.-274-5340G>T		intron_variant	Intron 3 of 8	ENST00000257749.9	NP_068585.1
BACH2	NM_001170794.2	c.-274-5340G>T		intron_variant	Intron 1 of 6		NP_001164265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BACH2	ENST00000257749.9	c.-274-5340G>T		intron_variant	Intron 3 of 8	1	NM_021813.4	ENSP00000257749.4

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115169 AN: 151928 Hom.: 44944 Cov.: 32

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.758 AC: 115299 AN: 152046 Hom.: 45011 Cov.: 32 AF XY: 0.755 AC XY: 56069 AN XY: 74286

African (AFR) AF: 0.943 AC: 39154 AN: 41532

American (AMR) AF: 0.782 AC: 11951 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 2539 AN: 3470

East Asian (EAS) AF: 0.604 AC: 3092 AN: 5122

South Asian (SAS) AF: 0.790 AC: 3811 AN: 4826

European-Finnish (FIN) AF: 0.546 AC: 5753 AN: 10534

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.683 AC: 46425 AN: 67976

Other (OTH) AF: 0.780 AC: 1643 AN: 2106

Alfa AF: 0.707 Hom.: 165492

Bravo AF: 0.782

Asia WGS AF: 0.731 AC: 2544 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.60
PhyloP100		-0.13
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: rs370409; hg19: chr6-90921740;