rs10944479

Variant names:

• chr6-90170674-G-A
• rs10944479
• NM_021813.4:c.-162+35895C>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+35895C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,174 control chromosomes in the GnomAD database, including 1,548 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 0.12 (1548 hom., cov: 32)
• Consequence: BACH2 NM_021813.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153
• Publications: 32 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=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 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.-162+35895C>T		intron	N/A	NP_068585.1	Q9BYV9
	BACH2	NM_001170794.2		c.-162+35895C>T		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.-162+35895C>T		intron	N/A	ENSP00000257749.4	Q9BYV9
	BACH2	ENST00000343122.7	TSL:5	c.-162+35895C>T		intron	N/A	ENSP00000345642.3	Q9BYV9
	BACH2	ENST00000406998.7	TSL:2	c.-162+35895C>T		intron	N/A	ENSP00000384145.3	Q9BYV9

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18674 AN: 152056 Hom.: 1546 Cov.: 32

Gnomad AFR AF: 0.0321

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0797

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.123 AC: 18675 AN: 152174 Hom.: 1548 Cov.: 32 AF XY: 0.117 AC XY: 8724 AN XY: 74390

African (AFR) AF: 0.0320 AC: 1328 AN: 41528

American (AMR) AF: 0.152 AC: 2319 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 368 AN: 3468

East Asian (EAS) AF: 0.00231 AC: 12 AN: 5190

South Asian (SAS) AF: 0.0806 AC: 389 AN: 4826

European-Finnish (FIN) AF: 0.114 AC: 1204 AN: 10578

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12558 AN: 67984

Other (OTH) AF: 0.122 AC: 258 AN: 2108

Alfa AF: 0.162 Hom.: 4058

Bravo AF: 0.123

Asia WGS AF: 0.0490 AC: 171 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.1
DANN	Benign	0.78
PhyloP100		0.15
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: rs10944479; hg19: chr6-90880393;