chr6-90248512-C-G

Variant names:

• chr6-90248512-C-G
• rs11755527
• NM_021813.4:c.-275+4001G>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.-275+4001G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 151,926 control chromosomes in the GnomAD database, including 11,074 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 0.37 (11074 hom., cov: 32)
• Consequence: BACH2 NM_021813.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.416
• Publications: 91 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: Ambry Genetics, Illumina, ClinGen, Labcorp Genetics (formerly Invitae)

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 (NFE) allele frequency at 95% confidence interval = 0.445 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BACH2	NM_021813.4	MANE Select	c.-275+4001G>C		intron	N/A	NP_068585.1	Q9BYV9
	BACH2	NM_001170794.2		c.-274-41831G>C		intron	N/A	NP_001164265.1	Q9BYV9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BACH2	ENST00000257749.9	TSL:1 MANE Select	c.-275+4001G>C		intron	N/A	ENSP00000257749.4	Q9BYV9
	BACH2	ENST00000343122.7	TSL:5	c.-269-41836G>C		intron	N/A	ENSP00000345642.3	Q9BYV9
	BACH2	ENST00000406998.7	TSL:2	c.-274-41831G>C		intron	N/A	ENSP00000384145.3	Q9BYV9

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56074 AN: 151808 Hom.: 11060 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.369 AC: 56107 AN: 151926 Hom.: 11074 Cov.: 32 AF XY: 0.366 AC XY: 27156 AN XY: 74206

African (AFR) AF: 0.215 AC: 8903 AN: 41414

American (AMR) AF: 0.398 AC: 6078 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1432 AN: 3468

East Asian (EAS) AF: 0.402 AC: 2078 AN: 5166

South Asian (SAS) AF: 0.416 AC: 1999 AN: 4804

European-Finnish (FIN) AF: 0.342 AC: 3598 AN: 10508

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30556 AN: 67974

Other (OTH) AF: 0.405 AC: 853 AN: 2108

Alfa AF: 0.431 Hom.: 7912

Bravo AF: 0.368

Asia WGS AF: 0.378 AC: 1318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.2
DANN	Benign	0.73
PhyloP100		0.42
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: rs11755527; hg19: chr6-90958231;