Genetic Variant NM_021813.4:c.*1636G>A (chr6-89930772-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021813.4(BACH2):c.*1636G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,522 control chromosomes in the GnomAD database, including 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 0.11 ( 971 hom., cov: 32)

Exomes 𝑓: 0.076 ( 2 hom. )

Consequence

BACH2
NM_021813.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.778

Publications

6 publications found

Variant links:

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

BACH2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 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.*1636G>A		3_prime_UTR	Exon 9 of 9	NP_068585.1
	BACH2	NM_001170794.2		c.*1636G>A		3_prime_UTR	Exon 7 of 7	NP_001164265.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BACH2	ENST00000257749.9	TSL:1 MANE Select	c.*1636G>A		3_prime_UTR	Exon 9 of 9	ENSP00000257749.4

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16124

AN:

152114

Hom.:

965

Cov.:

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.0914

Gnomad ASJ

AF:

0.0501

Gnomad EAS

AF:

0.0698

Gnomad SAS

AF:

0.0319

Gnomad FIN

AF:

0.0835

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0944

Gnomad OTH

AF:

0.110

GnomAD4 exome

AF:

0.0759

AC:

AN:

290

Hom.:

Cov.:

AF XY:

0.0604

AC XY:

AN XY:

182

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.0833

AC:

AN:

132

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0806

AC:

AN:

124

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0455

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.106

AC:

16160

AN:

152232

Hom.:

971

Cov.:

AF XY:

0.104

AC XY:

7749

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.156

AC:

6471

AN:

41516

American (AMR)

AF:

0.0912

AC:

1395

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0501

AC:

174

AN:

3470

East Asian (EAS)

AF:

0.0696

AC:

360

AN:

5176

South Asian (SAS)

AF:

0.0313

AC:

151

AN:

4826

European-Finnish (FIN)

AF:

0.0835

AC:

886

AN:

10606

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0944

AC:

6418

AN:

68022

Other (OTH)

AF:

0.113

AC:

238

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

754

1508

2262

3016

3770

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

336

504

672

840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0971

Hom.:

2594

Bravo

AF:

0.109

Asia WGS

AF:

0.0770

AC:

266

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

5.2

(source)

DANN

Benign

0.84

PhyloP100

0.78

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over