6-89941367-C-T

Variant names:

• chr6-89941367-C-T
• rs3734662
• NM_021813.4:c.1837-3017G>A

Variant summary

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

The NM_021813.4(BACH2):​c.1837-3017G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152,042 control chromosomes in the GnomAD database, including 16,017 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 0.45 (16017 hom., cov: 32)
• Consequence: BACH2 NM_021813.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141
• Publications: 8 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 (NFE) allele frequency at 95% confidence interval = 0.518 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.1837-3017G>A		intron	N/A	NP_068585.1
	BACH2	NM_001170794.2		c.1837-3017G>A		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.1837-3017G>A		intron	N/A	ENSP00000257749.4
	BACH2	ENST00000343122.7	TSL:5	c.1837-3017G>A		intron	N/A	ENSP00000345642.3
	BACH2	ENST00000406998.7	TSL:2	c.1837-3017G>A		intron	N/A	ENSP00000384145.3

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67730 AN: 151924 Hom.: 16017 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.0910

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.446 AC: 67752 AN: 152042 Hom.: 16017 Cov.: 32 AF XY: 0.442 AC XY: 32818 AN XY: 74326

African (AFR) AF: 0.349 AC: 14457 AN: 41466

American (AMR) AF: 0.472 AC: 7197 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1524 AN: 3470

East Asian (EAS) AF: 0.0910 AC: 471 AN: 5176

South Asian (SAS) AF: 0.431 AC: 2074 AN: 4814

European-Finnish (FIN) AF: 0.477 AC: 5047 AN: 10572

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.522 AC: 35495 AN: 67968

Other (OTH) AF: 0.436 AC: 919 AN: 2110

Alfa AF: 0.493 Hom.: 33271

Bravo AF: 0.436

Asia WGS AF: 0.276 AC: 957 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	3.9
DANN	Benign	0.46
PhyloP100		0.14
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: rs3734662; hg19: chr6-90651086;