chr6-90025265-A-G

Variant names:

• chr6-90025265-A-G
• rs7749730
• NM_021813.4:c.-12-16409T>C

Variant summary

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

The NM_021813.4(BACH2):​c.-12-16409T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,918 control chromosomes in the GnomAD database, including 15,175 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 0.42 (15175 hom., cov: 31)
• Consequence: BACH2 NM_021813.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BACH2	NM_021813.4	c.-12-16409T>C		intron_variant	Intron 5 of 8	ENST00000257749.9	NP_068585.1
BACH2	NM_001170794.2	c.-12-16409T>C		intron_variant	Intron 3 of 6		NP_001164265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BACH2	ENST00000257749.9	c.-12-16409T>C		intron_variant	Intron 5 of 8	1	NM_021813.4	ENSP00000257749.4

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63499 AN: 151800 Hom.: 15151 Cov.: 31

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.418 AC: 63566 AN: 151918 Hom.: 15175 Cov.: 31 AF XY: 0.415 AC XY: 30804 AN XY: 74270

African (AFR) AF: 0.665 AC: 27534 AN: 41432

American (AMR) AF: 0.431 AC: 6577 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1080 AN: 3470

East Asian (EAS) AF: 0.192 AC: 990 AN: 5152

South Asian (SAS) AF: 0.243 AC: 1171 AN: 4822

European-Finnish (FIN) AF: 0.324 AC: 3411 AN: 10544

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21613 AN: 67920

Other (OTH) AF: 0.421 AC: 889 AN: 2112

Alfa AF: 0.231 Hom.: 680

Bravo AF: 0.440

Asia WGS AF: 0.261 AC: 908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.4
DANN	Benign	0.47
PhyloP100		-0.046
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: rs7749730; hg19: chr6-90734984;