6-90119163-T-C

Variant names:

• chr6-90119163-T-C
• rs207270
• NM_021813.4:c.-161-30054A>G

Variant summary

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

The NM_021813.4(BACH2):​c.-161-30054A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 152,086 control chromosomes in the GnomAD database, including 18,197 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 0.48 (18197 hom., cov: 32)
• Consequence: BACH2 NM_021813.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103
• Publications: 10 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021813.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BACH2	NM_021813.4	MANE Select	c.-161-30054A>G		intron	N/A	NP_068585.1
	BACH2	NM_001170794.2		c.-161-30054A>G		intron	N/A	NP_001164265.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BACH2	ENST00000257749.9	TSL:1 MANE Select	c.-161-30054A>G		intron	N/A	ENSP00000257749.4
	BACH2	ENST00000343122.7	TSL:5	c.-161-30054A>G		intron	N/A	ENSP00000345642.3
	BACH2	ENST00000406998.7	TSL:2	c.-161-30054A>G		intron	N/A	ENSP00000384145.3

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73050 AN: 151968 Hom.: 18168 Cov.: 32

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.481 AC: 73133 AN: 152086 Hom.: 18197 Cov.: 32 AF XY: 0.478 AC XY: 35568 AN XY: 74362

African (AFR) AF: 0.563 AC: 23372 AN: 41480

American (AMR) AF: 0.542 AC: 8268 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1606 AN: 3468

East Asian (EAS) AF: 0.130 AC: 674 AN: 5182

South Asian (SAS) AF: 0.504 AC: 2432 AN: 4824

European-Finnish (FIN) AF: 0.390 AC: 4129 AN: 10578

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31044 AN: 67972

Other (OTH) AF: 0.477 AC: 1005 AN: 2108

Alfa AF: 0.451 Hom.: 18095

Bravo AF: 0.494

Asia WGS AF: 0.350 AC: 1219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.0
DANN	Benign	0.82
PhyloP100		0.10
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: rs207270; hg19: chr6-90828882;