6-89971747-A-C

Variant names:

• chr6-89971747-A-C
• rs6917758
• NM_021813.4:c.244-19885T>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.244-19885T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,170 control chromosomes in the GnomAD database, including 4,364 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 0.22 (4364 hom., cov: 32)
• Consequence: BACH2 NM_021813.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597
• Publications: 0 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.286 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.244-19885T>G		intron	N/A	NP_068585.1
	BACH2	NM_001170794.2		c.244-19885T>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.244-19885T>G		intron	N/A	ENSP00000257749.4
	BACH2	ENST00000343122.7	TSL:5	c.244-19885T>G		intron	N/A	ENSP00000345642.3
	BACH2	ENST00000406998.7	TSL:2	c.244-19885T>G		intron	N/A	ENSP00000384145.3

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34234 AN: 152052 Hom.: 4367 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.0244

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.225 AC: 34228 AN: 152170 Hom.: 4364 Cov.: 32 AF XY: 0.224 AC XY: 16664 AN XY: 74360

African (AFR) AF: 0.125 AC: 5175 AN: 41548

American (AMR) AF: 0.197 AC: 3018 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1043 AN: 3468

East Asian (EAS) AF: 0.0241 AC: 125 AN: 5184

South Asian (SAS) AF: 0.259 AC: 1247 AN: 4814

European-Finnish (FIN) AF: 0.291 AC: 3076 AN: 10566

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19680 AN: 67984

Other (OTH) AF: 0.253 AC: 535 AN: 2112

Alfa AF: 0.220 Hom.: 2616

Bravo AF: 0.213

Asia WGS AF: 0.168 AC: 581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.8
DANN	Benign	0.68
PhyloP100		-0.60
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: rs6917758; hg19: chr6-90681466; COSMIC: COSV57605611;