6-90247744-C-T

Variant names:

• chr6-90247744-C-T
• rs3757247
• NM_021813.4:c.-275+4769G>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.-275+4769G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 151,962 control chromosomes in the GnomAD database, including 12,045 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 0.38 (12045 hom., cov: 31)
• Consequence: BACH2 NM_021813.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177
• Publications: 68 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BACH2	NM_021813.4	c.-275+4769G>A		intron_variant	Intron 3 of 8	ENST00000257749.9	NP_068585.1
BACH2	NM_001170794.2	c.-274-41063G>A		intron_variant	Intron 1 of 6		NP_001164265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BACH2	ENST00000257749.9	c.-275+4769G>A		intron_variant	Intron 3 of 8	1	NM_021813.4	ENSP00000257749.4

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58295 AN: 151844 Hom.: 12026 Cov.: 31

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.384 AC: 58343 AN: 151962 Hom.: 12045 Cov.: 31 AF XY: 0.381 AC XY: 28317 AN XY: 74254

African (AFR) AF: 0.217 AC: 8997 AN: 41480

American (AMR) AF: 0.427 AC: 6516 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1516 AN: 3466

East Asian (EAS) AF: 0.473 AC: 2435 AN: 5146

South Asian (SAS) AF: 0.443 AC: 2133 AN: 4814

European-Finnish (FIN) AF: 0.358 AC: 3776 AN: 10542

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31434 AN: 67944

Other (OTH) AF: 0.434 AC: 914 AN: 2106

Alfa AF: 0.441 Hom.: 65328

Bravo AF: 0.383

Asia WGS AF: 0.462 AC: 1609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.30
PhyloP100		0.18
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: rs3757247; hg19: chr6-90957463;