6-90259230-C-T

Variant names:

• chr6-90259230-C-T
• rs619192
• NM_021813.4:c.-352-6640G>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.-352-6640G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 152,100 control chromosomes in the GnomAD database, including 34,973 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 0.67 (34973 hom., cov: 32)
• Consequence: BACH2 NM_021813.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.863
• Publications: 9 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BACH2	NM_021813.4	c.-352-6640G>A		intron_variant	Intron 2 of 8	ENST00000257749.9	NP_068585.1
BACH2	NM_001170794.2	c.-275+37250G>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.-352-6640G>A		intron_variant	Intron 2 of 8	1	NM_021813.4	ENSP00000257749.4

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101402 AN: 151982 Hom.: 34931 Cov.: 32

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.667 AC: 101489 AN: 152100 Hom.: 34973 Cov.: 32 AF XY: 0.662 AC XY: 49250 AN XY: 74340

African (AFR) AF: 0.846 AC: 35101 AN: 41512

American (AMR) AF: 0.648 AC: 9898 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1984 AN: 3470

East Asian (EAS) AF: 0.472 AC: 2435 AN: 5162

South Asian (SAS) AF: 0.658 AC: 3176 AN: 4826

European-Finnish (FIN) AF: 0.500 AC: 5278 AN: 10560

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.608 AC: 41352 AN: 67966

Other (OTH) AF: 0.675 AC: 1425 AN: 2112

Alfa AF: 0.592 Hom.: 5268

Bravo AF: 0.685

Asia WGS AF: 0.576 AC: 2006 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.64
DANN	Benign	0.59
PhyloP100		-0.86
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: rs619192; hg19: chr6-90968949;